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Agarwal A, Desai NR, Mahfouz R, Mouradi R, Sharma R, Sabanegh E. Investigating physiologic effects of cell phone radiation on human spermatozoa:use of a novel in vitro model. Fertil Steril 2009;90,suppl 1:S221.
Sperm were exposed to cell phone radiation in vitro. Exposed samples showed decreased motility and viability and an 18% increase of reactive oxygen species. Use of a blue-tooth devise with the cell phone in the front pocket should be avoided, although antioxidants could be helpful in ameliorating such an effect. This study was done by one of the foremost U.S. authorities on oxidative damage to sperm.
Attaman JA, Toth TL, Furtado J, Campos H, Hauser R, Chavaro JE. Dietary fat and semen quality among men attending a fertility clinic. Human Reproduction. 2012;2:1466-74.
Men in the highest third of fat intake had a 43% lower total sperm count than men in the lowest third, and that appeared to be due to saturated fat intake. Higher intake of omega-3 fatty acids was related to improved strict morphology, with the highest third of intake having 1.9% higher morphology than those with the lowest third. See also Safarinejad, 2011. PMID: 22416013
Balercia G, Mosca F, Mantero F, Boscaro M, Mancini A, Ricciardo-Lamonica G, et al. CoenzymeQ10supplementation in infertile men with idiopathic asthenoozospermia: an open, uncontrolled pilot study. Fertil Steril 2004;81:93-8.
Coenzyme Q-10 was given to 22 men (200 mg twice daily) with reduced sperm motility for 6 months followed by 6 months wash-out. The seminal levels of Q-10 tripled and the percentage of forwardly progressive sperm increased from 9.1 to 16.3 and returned to 9.5 after 6 months off treatment. Curvilinear velocity increased from 26 to 46% with treatment. Although this study was not placebo-controlled, the return to baseline following discontinuation of the Q-10 argues for a true effect. The motility of the sperm is directly related to the energy produced by sperm mitochondria, so such a therapeutic response was predicted (see Bentov, 2010). Because Q-10 is itself an antioxidant, it is difficult to separate a direct effect on the generation of energy by the mitochondria from a non-specific effect due to its antioxidant properties. PMID: 14711549
Bentov Y, Esfandiari N, Burstein E, Casper RF. The use of mitochondrial nutrients to improve the outcome of fertility treatment in older patients. Fertil Steril 2010;93:272-5.
This paper proposes that the use of co-enzyme Q-10 could improve egg and embryo quality in older infertile women. The oocyte has very high levels of energy producing mitochondria, and oocyte mitochondrial DNA increases enormously during follicular growth. The energy present in the mature egg is necessary for the proper segregation of chromosomes as they divide and are organized so that the appropriate number of chromosomes is present when the egg becomes fertilized. Likewise, a high level of energy is required for cell division into an embryo and by the rapidly dividing embryo. The mitochondrial DNA existing in the fully mature oocyte must be sufficient for the many cells of the embryo to function and continue to divide, because mitochondria do not replicate until the blastocyst stage. The older egg has lower levels of mitochondrial DNA and energy. Co-enzyme Q-10 is critical to the transport of electrons and protons involved in the chemical reactions that drive ATP and therefore energy production. This mitochondrial nutrient has been shown to reverse the effects of aging on the oocyte in the older female rat, including improved chromosome segregation. Although not yet evaluated in the older human female to improve fertility, supplements of Q-10 have been used in a number of other studies with no side effects or adverse events being reported. PMID: 19732879
Chavarro JE, Furtado J, Toth TL, Ford J, Campos H, Hauser R. Sperm fatty acid composition and its relationship with sperm concentration among men attending an infertility clinic. Fertil Steril 2009;90,Suppl 1:S42.
A very strong correlation was found between sperm concentration and sperm omega-3 fatty acids, while there was a strong negative correlation with trans fats. While it is possible that these findings simply relate to poor dietary intake of other nutrients such as antioxidants, these fats do influence cell membrane function, which is very important for sperm (Walthes). Also, antioxidants predominantly influence sperm motility rather than sperm count. It is also possible that the effect of omega-3’s was through increasing testicular blood flow.
Chavarro JE Colaci DS, Afeiche M, Gaskins, AJ, Write D, Toth TL, et al. Dietary fat intake and in-vitro fertilization outcomes: saturated fat intake is associated with fewer metaphase 2 oocytes. Hum Reprod 2012;suppl O-200.
In multivariate-adjusted regression models, higher intakes of total fat and saturated fat were related to fewer metaphase 2 (M2) oocytes retrieved. This association was driven by intake of saturated fat. Women in the highest third of saturated fat intake had, on average, 9.3 (95%CI: 5.9-14.7) mature oocytes while women reporting the lowest intake had 11.6 (95%CI: 8.1-16.7) mature oocytes, (p-trend = 0.03). Polyunsaturated fat consumption was inversely related to embryo quality. Women in the highest third of polyunsaturated fat intake, had a higher proportion of poor quality embryos (p-trend = 0.02) and slow cleaving embryos (p-trend = 0.001) than women in the lowest third of intake. In addition, higher trans fat consumption was associated with a lower proportion of accelerated cleavage embryos (p-trend = 0.03). Higher intakes of monounsaturated fat were related to higher odds of live birth. The odds ratio of a live birth among women with the highest intake of mono-unsaturated fat was 3.45 (95%CI: 1.12-10.62) when compared to women with the lowest intake (p-trend: 0.03).
De la Rochebrochard E, de Mouzon J, Thepot F, Thonneau P, French National IVF Registry (FIVNAT) Association. Fathers over 40 and increased failure to conceive: the lessons of in vitro fertilization in France. Fertil Steril 2006;85:1420-4.
In this large study there was a two-fold risk of failure due to the man’s age being over 40, and the risk appeared to further increase as the female’s age increased. Sperm fragmentation increases with male age (Schmid, 2007). It is reasonable to suggest high dose vitamin C and E (Greco, 2005) for all men over age 40 for two months prior to IVF.
Patients were randomized before IVF but most had attended no or only a few sessions before the first cycle. In the group having intensive cognitive and behavioral intervention, 52% conceived in their second cycle of IVF (in spite of 39% of subjects having completed only 1-5 sessions) compared to 20% in the control group (p < 0.05). The mind/body program is the most intensive and successful stress reduction program yet devised for infertile couples. PMID: 21496800
Ebbesen SM, Zachariae R, Mehlsen MY, Thomsen D, Hojgaard A, Ottosen L, et al. Stressful life events are associated with a poor in-vitro fertilization (IVF) outcome: a prospective study. Hum Reprod 2009;24:2173-82.
809 women recorded recent stressful life events within the 12 months prior to IVF. Using logistic regression, the number of negative life events predicted IVF failure (OR 0.89, p = 0.02) and mediation analysis indicated fewer oocytes were retrieved. Patients ideally should do IVF well after any very stressful life event and during a time when their current stress is at a minimum. PMID: 19465459
IVF patients were randomized to the antioxidant, N-acetyl cysteine (NAC), or no additional treatment. Granulosa cell apoptosis (a measure of cell viability) was significantly lower with NAC; The pregnancy rate was non-significantly higher with NAC but the study was not large enough to examine that outcome. Lower apoptosis was associated with higher fertilization, better quality embryos and a higher pregnancy rate. Antioxidants vary in potency and in their effects in various tissues. Also, a variety of different antioxidants may yield better tissue protection than only one. The very strong relationship of granulosa cell health to pregnancy was confirmed. PMID: 20385511
Esbert M, Riqueros M, Florensa M, Mugica A, Ballesteros A, Calderon G. Influence of male aging on sperm parameters and over egg donation program results. Fertil Steril 2009,suppl 1;90:S73.
This study using young egg donors has confirmed the significant effect of male age on successful pregnancy. Male age had a negative correlation with pregnancy (p = .021) and implantation (p = 0.002).
Facchinetti F, Matteo ML, Artini GP, Volpe A, Genazzani JR. An increased vulnerability to stress is associated with a poor outcome of in vitro fertilization-embryo transfer treatment. Fertil Steril 1997;67:309-14.
When subjects were tested for their blood pressure and heart rate responses to stressful visual and auditory stimuli, the chance of becoming pregnant with IVF was associated with lesser physiologic responses to stress. It appears that not only external sources of stress reduce IVF outcome, but also an exaggerated physiologic response to stress leads to unfavorable outcomes. PMID: 9022608
Fratterelli JL, Miller KA, Miller BT, Elkind-Hirsch K, Scott T. Male age negatively impacts embryo development and reproductive outcome in donor ocyte assisted reproductive technology cycles. Fertil Steril 2008;90:97-103.
Male age over 50 significantly reduced pregnancy and blastocyst formation rates, although embryo morphology through the cleavage stage was not affected. The fetal genes only become active after day 3, so these results implicate increased DNA fragmentation in the reduced outcome with increasing male age. PMID: 17765235
Girsh E, Katz N, Genkin L, Girtler O, Bocker J, Bezdin S, et al. Male age influences oocyte-donor program results. J Assist Reprod Genet 2008;25:137-43.
Increasing male age was associated with a lower pregnancy rate, decreased sperm morphology, and reduced day 3 embryo quality. Although the embryo's genes do not become active until after day 3, the sperm do contribute to the apparatus involved in cell division, which could affect earlier cleavage stages. PMID: 18392674
Goldberg T, Cai W, Peppa M, Dardaine V, Baliga BS, Uribarri J, et al. Advanced glycation end products in commonly consumed foods. J Am Diet Assoc 2004;104:1287-91.
250 foods were tested for a marker of advanced glycation end products. High fat foods and meat contained the highest levels, and broiling, frying, roasting, higher temperature, and longer cooking times were associated with higher food levels of AGE's. PMID: 15281050
Greco E, Iacobelli M, Rienzi L, Ubaldi F, Ferrero S, Tesarik J. Reduction of the incidence of sperm fragmentation by oral antioxidant treatment. J Androl 2005;26:349-53.
Sixty-four men with unexplained infertility and with more than 15% sperm fragmentation took 1 gm of vitamin C and 1 gram of vitamin E or placebo for two months. In the treatment group fragmentation decreased from 22 to 9% (p < 0.001). Sperm numbers increased from 19 to 28%, but there was a slight decrease of the percentage of normal sperm (from 10.5 to 8 %, p < 0.05). It seems unlikely that the small decrease of morphology which was of borderline significance is a true finding, because another strong antioxidant, pycnogenol, was found to significantly increase the percentage of morphologically normal sperm (Stanislovov, 2009). PMID: 15867002
Green RJ, Murphy AS, Schulz B, Watkins BA, Ferruzi MG. Common tea formulations modulate in vitro digestive recovery of green tea catechins. Mol Nutr Food Res 2007;51:1152-62.
Adding vitamin C to green tea protected the polyphenols in green tea during absorption, with total catechin recovery increasing about three-fold, while recovery of EGCG (thought to be the main anti-cancer factor in green tea) increased over ten-fold. The dose required for a 6 oz cup of tea would be 25 to 50 mg. PMID: 17688297
Mahfouz R, Sharma R, Thiyagarjan A, Kale V, Gupta S, Sabanegh E, et al. Sperm characteristics and DNA fragmentation in infertile men with low and high levels of seminal reactive oxygen species. Fertil Steril 2010;94:2141-6.
Semen samples from 100 infertile men were examined for reactive oxygen species (ROS), DNA fragmentation, and motility. Men with reduced motility had higher ROS and increased DNA fragmentation. This is yet another study showing the harmful effects of ROS on both sperm motility and DNA fragmentation. PMID: 20117780
Hakim RB, Gray RH, Zacur H. Alcohol and caffeine consumption and decreased fertility. Fertil Steril 1998; 70:632-7.
Alcohol decreased the chance of pregnancy by over 50% (odds ratio 0.43, 0.25-0.76), there was a greater effect with more alcohol, and the effect was worse with any alcohol together with caffeine. PMID: 9797089
Halvorsen BL, Carlsen MH, Phillips KM, Bohn SK, Holte K, Jacobs DR, et al. Content of redox-active compounds (ie, antioxidants) in foods consumed in the United States. Am J Clin Nutr 2006;84:95-135.
This exhaustive compilation of total antioxidant content of common foods consumed in the U.S. showed that on the basis of typical serving sizes, blackberries, walnuts, strawberries, artichokes, cranberries, brewed coffee, raspberries, pecans, blueberries, ground cloves, grape juice, and unsweetened baking chocolate were at the top of the ranked list. Other spices such as oregano, ginger, cinnamon, turmeric and basil ranked high but large amounts are not generally added to foods. Red wine, toasted whole wheat bread and bran flakes were also good sources. Cooking almost without exception increased antioxidant content. Brewed green tea was not examined. Virtually all fruits and vegetables were sources of antioxidants, but at much lower levels than the ones listed above. Importantly, this study does not take into account the factors in foods with special properties such as the anti-cancer effects of broccoli, spinach, and green tea, nor the fiber that is linked to reduced cancer and heart disease. It also does not take into account factors influencing absorption of various compounds such as the effect of vitamin C in enhancing absorption of the antioxidants in green tea. Furthermore, certain antioxidants may have a greater influence on nitric oxide production than others, so foods such as pomegranate, blueberries, chocolate, green tea and red wine, and supplements such as pycnogenol that have been shown to increase NO and its biologic effects on blood vessels deserve special emphasis. PMID: 16825686
Hughes EG, Yeo J, Claman P, Younglai EV, Sagle MA, Daya S, Collins JA. Cigarette smoking and the outcomes of in vitro fertilization: measurement of effect size and levels of action. Fertil Steril 1994; 62:807.
Meta-analysis showed a reduced odds ratio for successful pregnancy for women who smoked (.54, CL .385-.757). Various other studies have shown reduced ovarian reserve, ovarian response, and an increased miscarriage rate. Cigarette smoking has such a dramatic effect on fertility that for anyone to continue to smoke while trying to conceive is self-defeating and completely illogical. Second-hand smoke must also be avoided (Neal, 2005). PMID: 7926092
Jadeon JE, Ben-ami N, Haddad S, Radin O, Bar-ami S, Younis JS. Prospective evaluation of early follicular ovarian stromal blood flow in infertile women undergoing IVF-ET treatment. Gynecol Endocrinol 2012;28:356-9. PMID 22456029
Ovarian blood flow correlated with the number of follicles developing in response to stimulation and resistance to flow correlated negatively with the number of resting follicles.
Janesch A, McCallie B, Parks, J, Schoolcraft WB, Gardner DK, Katz-Jaffe MG. Impact of high protein diet on mouse oogenesis. Fertil Steril 2009,90,suppl 1:S217.
A high protein diet was found to cause dysregulation of 248 genes in mouse MII oocytes. Not only does a high protein diet cause abnormal oocyte gene function, but it alters the fallopian tube environment causing disordered imprinting of genes. Some of these effects are due to accumulation of ammonia from protein metabolism. High protein diets such as the Atkins diet should be avoided in infertile women.
Jinno M, Takeuchi M, Wataabe A, Teruya K, Hirohama J, Eguchi N, et al. Advanced glycation end-products accumulation compromises embryonic development and achievement of pregnancy by assisted reproductive technology. Hum Reprod 2011;26:604-11.
Higher levels of advanced glycation end products (AGE’s) in serum correlated with reduced follicular and embryonic development and a lower likelihood of ongoing pregnancy. AGE’s are potent oxidants and toxic chemicals created when food is cooked at high heat such as grilling and barbequing and they accumulate with age. They also are increased with higher blood glucose and therefore in diabetics and with obesity. Avoiding cooking of foods at a high heat, reducing sugar intake and body weight, and maintaining a high intake of antioxidants may help to counter such effects. PMID: 21233108
Klonoff-Cohen H, Bleha J, Lam-Kruglick P. A prospective study of the effects of female and male caffeine consumption on the reproductive endpoints of IVF and gamete intra-Fallopian transfer. Hum Reprod 2002;17:1746-54.
221 women were studied prospectively before IVF or GIFT. Minimal caffeine (0-2 mg = 1 cup of decaffeinated tea or coffee) was associated with a higher chance of pregnancy. PMID: 12093834
Klonoff-Cohen H, Chu E, Natarajan L, Sieber W. A prospective study of stress among women undergoing in vitro fertilization or gamete intrafallopian transfer. Fertil Steril 2001;76:675-87.
151 women having IVF or gamete intra-fallopian transfer (GIFT) were followed prospectively. Positive affect (lack of depression) was associated with number of oocytes retrieved, embryos transferred and live births. PMID: 11591398
Klonoff-Cohen H, Lam-Kruglick P, Gonzolez C. Effects of maternal and paternal alcohol consumption on the success rates of in vitro fertilization and gamete intrafallopian transfer. Fertil Steril 2003;79:330-9.
In a multicenter trial of 221 couples having IVF, multivariate logistic regression showed a 13% reduction in the number of eggs in women consuming alcohol. The risk of not becoming pregnant increased by 2.9 (0.99-8.24) and miscarriage increased by 2.2 (1.1-4.5). For alcohol intake by the male, there was over a two-fold decrease of pregnancy and over a two-fold increase of miscarriage. The best advice is for both partners to avoid alcohol when trying to conceive. PMID: 12568842
Koskimaki J, Shiri R, Tammela T, Hakkinen J, Hakama M, Auvinen A. Regular Intercourse Protects Against Erectile Dysfunction: Tampere Aging Male Urologic Study. Amer J Med. 2008;121:592-596.
In a study of men 55 to 75 years of age, a two-fold incidence of ED was noted with less frequent coitus. PMID: 18538297
Lozano DH, Frydman N, Levaillant JM, Fay S, Frydman R, Fanchin R. The 3D vascular status of the follicle after HCG administration is qualitatively rather than quantitatively associated with its reproductive competence. Hum Reprod 2007;22:1095-9.
When the (blood) flow index surrounding the single mature follicle by 3-D doppler was high, the pregnancy rate was significantly increased (33 versus 4%, p < 0.009). This striking relationship of blood flow to the occurrence of pregnancy argues very strongly that blood flow, and therefore nutrients and oxygen, are critical to egg and embryo competence. The egg is an extremely large cell and during its maturation it becomes more and more distant from the circulation surrounding the follicle. The chromosomes are undergoing reorganization at the very end of this process, and most chromosomal abnormalities are due to disorganized chromosome segregation at this late stage of egg development. PMID: 17179201
Luke B, Brown MB, Missmer SA, Bukulmez O, Leach R, Stern JE. The effect of increasing obesity on the response to and outcome of assisted reproductive technology: a national study. Fertil Steril 2011;96;820-5.
In this study of almost over 150,000 ART cycles, women were classified as overweight, or having class I, II, or III obesity. The increased chance of failing to achieve a clinical pregnancy and live birth for overweight (BMI 25-29.9) were 3 and 10%, for class I obesity (BMI 30-34.9) were 14 and 25%, class II (35-39.9) were 26 and 34% and class III and above (>39.9) were 41-53% and 39-229%. The chance of having a stillbirth for obese women was two-fold higher. While there is just a mild increase of pregnancy loss for women whose BMI is 25-29.9, as weight further increases, the chance of a successful birth progressively falls, with the most prominent effect being when the BMI is over 35. PMID: 21821244
Luke B, Brown MB, Missmer SA, Bukulmez O, Leach R, Stern JE. A national study of the effect of increasing obesity on the response to and outcome of assisted reproductive technology (ART). Fertil Steril 2010;94:suppl S52.
Even with a successful birth, the odds of delivering before 32 weeks, which is quite premature, increases by 26% when the BMI is over 30, and by over 50% when the BMI is over 35. Such early delivery can lead to severe problems in the nursery with a marked increase of the chance of the new born not surviving or having very significant health problems or permanent handicaps which sometimes can be severe. The mechanisms of these effects are not known, but increased inflammation and oxidative stress are likely candidates.
Luke (2011b) B, Brown MB, Stern JE, Missmer SA, Fujimoto VY, Leach R. Racial and ethnic disparities in assisted reproductive technology pregnancy and live birth rates within body mass index categories. Fertil Steril 2011;95:1661-6.
For non-white obese women having IVF, the chances of failing to conceive and delivery are 86% greater than for Caucasian women. The reasons behind these ethnic differences are not understood, but both endocrine and uterine factors are suspected. Estradiol levels during stimulation are higher in Asian and African American women, and both have an increased occurrence of uterine fibroids. PMID: 21269616
Mendiola J, Torres-Cantero AM, Vioque J, Moreno-Grau JM, Ten J, Roca M, et al. A low intake of antioxidant nutrients is associated with poor semen quality in patients attending fertility clinics. Fertil Steril 2010;93:1128-33.
Infertile men with poor semen quality had a significantly lower intake of dietary antioxidants. This study ties in nicely with the observation that antioxidant treatment improves semen quality (Stanislovov, 2009), and that poor semen quality is associated with a low level of antioxidant capacity. PMID: 19147135
Mok-Lin E, Erlich S, Williams PL, Petrozza J, Wright D, Calafat AM, et al. Urinary bisphenol A concentrations and ovarian response among women undergoing IVF. Int J Androl 2010;33:385-93.
Bisphenol A, a toxic endocrine disruptor that leaches out of plastic water bottles and food can linings, was measured in the urine of women having IVF. The concentrations were inversely correlated with the number of oocytes retrieved (p < 0.01). The type of plastics having any contact with food or drink should be checked. If it is a #2 HDPE (high density polyethylene), or a #4 LDPE (low density polyethylene), or a #5 PP (polypropylene), your container is fine. Bisphenol mainly leaches from #7 plastic (polycarbonate) and leaching is markedly increased with heating. If you can smell or taste plastic, you’re eating or drinking it. See PMID: 20002217
Morris SN, Missmer SA, Cramer DW, Powers RD, McShane PM, Hornstein MD. Effects of lifetime exercise on the outcome of in vitro fertilization. Obstet Gynecol 2006;108:938-45.
More than three hours of aerobic exercise was associated with a decreased success rate with IVF. Of course it could be that more anxious and stressed patients exercise more, but it is also possible that the stress of exercise could add together with the stress of infertility and cause such an effect. The authors did not separate out the effect of exercise before versus during IVF. Until more studies are done, it may be prudent to advise only a 30 minute brisk walk most days of the week for patients undergoing fertility treatments, particularly IVF. PMID: 17012457
Neal MS, Hughes EG, Holloway AC, Foster WG. Sidestream smoking is equally as damaging as mainstream smoking on IVF outcomes. Hum Reprod 2005;20:2531-5.
The pregnancy rate with IVF was similarly and significantly reduced when the female was exposed to side-stream smoke (20%) as with smoking (19.4%), compared to non-smokers (43.8%) (p < 0.001). PMID: 15919779
Quant HS, Tirado E, Baca Q, Leader B, Penzias AS. Sperm DNA fragmentation index worsens with advancing age. Fertil Steril 2009;90,suppl 1:S72.
Sperm DNA fragmentation remained at a mean of 13-16% in men under age 40, with a gradual increased percentage of men having levels over 30% (6.5 increasing to 9.5%), but the mean in men 41-45 rose to 19% with 18% over 30% fragmentation, and in men over age 45 the mean increased to 24% and 26% had over 30% fragmentation. This study indicated that sperm fragmentation testing is most helpful after age 40, and that routine antioxidant supplementation is reasonable for all men over age 40. The antioxidant capacity of semen decreases with age. There may be a commonality with the rising incidence of erectile dysfunction with age in men over age 40. Men with erectile dysfunction have a lower intracellular level of antioxidant, and pycnogenol, a potent proanthocyanidin antioxidant improves ED (Stanislavov, 2008).
Rossi BV, Berry KF, Hornstein MD, Cramer, DW, Ehrlich S, Missmer SA. The effect of alcohol consumption on in vitro fertilization. Obstet Gynecol 2011;117:136-42.
In an analysis of over 5,000 cycles, there was a negative effect of alcohol for both partners. For women drinking white wine the odds ratio was 0.50 (CL .27-.93); for men drinking beer the odds ratio was 0.67 (CL .45-.94). The best advice is for both partners to avoid alcohol when trying to conceive, particularly when undergoing IVF. PMID: 21173655
Safarinejad MR. Effect of omega-3 polyunsaturated fatty acid supplementation on semen profile and anti-oxidant capacity of seminal plasma in infertile men with idiopathic oligoasthenoteratospermia: a double-blind, placebo-controlled, randomized study. Andrologia 2011;43:38-47.
Supplementation with 1840 mg of omega-3's (EPA and DHA) for 32 weeks increased sperm morphology, and also sperm concentration and motility. Although lower doses were not examined, it is reasonable to recommend 1,000-2,000 mg of omega-3's for men with low strict morphology. PMID: 21219381
Sanders KA, Bruce NW. Psychosocial stress and treatment outcome following assisted reproductive technology. Hum Reprod 1999;14:1656-1662.
In a study of 90 women followed prospectively, univariate analysis found a negative impact of full-time employment, hostile mood, and higher anxiety on successful outcome of IVF. Multiple regression analysis also found depression to be a negative factor. PMID: 10357996
Schmid TE, Eskenazi B, Baumgartner A, Marchetti F, Young S, Weldon R, et al. The effects of male age on sperm DNA damage in healthy non-smokers. Hum Reprod 2007;22:180-7.
This study showed a progressive increase of fragmented DNA of sperm with increasing age. Fragmentation was also higher for men who consumed more than 3 cups of coffee per day. Interestingly the increased fragmentation with age was detected only under alkaline conditions, suggesting that not all assays may detect this effect of age, yet it could be an important or even the entire reason for increased pregnancy failure (and the slight increase of genetic abnormalities) due to male age (De la Rochebrochard, 2006). For this reason, it is reasonable to suggest high antioxidant intake (Greco, 2005) for all men over age 40 for two months prior to IVF. PMID: 17053003
Schwedhelm E, Maas R, Freese R, Jung D, Lukacs Z, Jambrecina A, et al. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol 2008;65:51-9.
The circulating level of L-arginine, the direct precursor of NO, is over twice as high after ingestion of L-citruline compared to ingestion of L-arginine. L-citrulline also acts within the cell as a precursor of L-arginine. Because 5 gm of L-arginine orally per day benefits ED, 2 gm of L-citrulline should have a similar effect. Also, for men with reduced semen quality, 1.5-2 gm of L-citrulline can be substituted for 3 gm of L-arginine (Stanislavov, 2009). PMID: 17662090
Smeenk JMJ, Verhaak CM, Eugster A, van Minnen A, Zielhuis GA, Braat DD. The effect of anxiety and depression on the outcome of in-vitro fertilization. Hum Reprod 2001;16:1420-3.
In a study of 291 women having IVF/intracytoplasmic sperm injection (ICSI) using the State and Trait Anxiety Inventory and Beck Depression Inventory and multiple logistic regression, state anxiety (p = 0.01) and depression (p = 0.03) were correlated with failure. PMID: 11425823
Soares SR, Simon C, Remohí J, Pellicer A. Cigarette smoking affects uterine receptiveness. Hum Reprod 2007;22:543-7.
In a study of 785 egg donation cycles with a non-smoking male, heavy smoking in the female recipient (> 10 cigarettes per day) was associated with a lower pregnancy rate (34.1% vs 52.2%, p = 0.02). PMID:17095517
This study showed a highly significant benefit on erectile function of a four week treatment of 80 mg of pycnogenol and 3 gm of L-arginine daily. The use of two supplements makes it difficult to determine which contributed to the results. One must assume that each contributed to the effects observed. Interestingly, the treatment also significantly raised testosterone levels and improved semen quality (Stanislavov, 2009). PMID: 17703218
Stanislavov R, Nikolova V, Rohdewald P. Improvement of seminal parameters with Prelox: A randomized, double-blind, placebo-controlled, crossover trial. Phytother Res 2009;23:297-302.
In this well-controlled trial, 3 gm of L-arginine and 80 mg of pycnogenol was associated with significant increases of semen volume, sperm density, percent motile sperm, and percent normal morphology. This could be due to improved testicular blood flow, to the strong antioxidant potency of pycnogenol, and/or to a direct effect on the testosterone-producing testicular cells with testosterone then promoting more normal sperm production (Stanislovov, 2008). With the exception of high dose vitamin C and E, this is one of the very few studies of any supplements found to cause such a clear improvement of semen parameters in infertile men. This study should have been in the Journal of Andrology, Fertility and Sterility or Human Reproduction. PMID: 19142978
Suh CS, Jee BC, Choi YM, Kim JG, Lee JY, Moon SY. Prognostic implication of apoptosis in human luteinized granulosa cells during IVF-ET. J Assist Reprod Genetics 2002;19:209-14.
The authors examined apoptosis as an indicator of the function and viability of the granulosa cells (the cells surrounding and nourishing the egg) and found that the level was about three-fold lower in women who did not conceive (p < 0.0001). Of the myriad of factors that have been measured in the fluid and cells surrounding the egg, this has been the single most dramatic and statistically significant finding, and one that has been consistently found by other investigators. Increased apoptosis (programmed cell death) is an indicator of poor cellular function, and the granulosa cells are critical to the health of the oocyte and therefore the embryo. PMID: 12099550
Tirado EE, Rivnay B, Marquette ML, Bourque V, Araneo C, Leader BS. Age is highly correlated with oxidative damage in sperm from infertile males. Fertil Steril 2009,90,suppl 1;S220.
Semen from 150 infertile males was analyzed for lipid peroxidation (LPO, an indicator of oxidative damage to sperm cell membranes) and DFI scores (an index of sperm DNA fragmentation). LPO increased steadily from 4.0 in men 20-29 to 12.4 in men 50-59. Levels doubled in the usual 30-50 age range of infertile males having IVF. DFI likewise increased from 16 to 38, with men 30-50 having a doubling of their scores. The increase of these two parameters was not entirely parallel. Comment: Two months of a gm of vitamin C and 1000 IU of vitamin E reduced the fragmentation score from 22 to 9 % compared to no change with placebo, suggesting that antioxidant capacity and sperm DNA damage are linked. All infertile men should be advised to increase their antioxidant intake.
Twigt JM, Bolhuis MEC, Steegers EAP, Hammiche F, van Inzen WG, Laven JSE, Steegers-Theunissen RPM. The preconception diet is associated with the chance of ongoing pregnancy in women undergoing IVF/ICSI treatment. Hum Reprod 2012;27:2526-31.
Adherence to the diet recommended by the Netherlands Nutrition center was associated with a 65% increase in the chance of ongoing pregnancy. PMID: 22593431
Vaamonde D, Da Silva-Grigoletto ME, Garcia-Manso JM, Barrera N, Vaamonde-Lemos R. Physically active men show better semen parameters and hormone values than sedentary men. Eur J Appl Physiol 2012;112:3267-73. PMID:22234399
Moderate activity improved sperm quality.
Vujkovic M, de Vries JH, Lindemans J, Macklon NS, van der Spek PJ, Steegers-Theunissen RPM. The preconception Mediterranean dietary pattern in couples undergoing in vitro fertilization/intracytoplasmic sperm injection treatment increases the chance of pregnancy. Fertil Steril 2010;94:2096-101.
High adherance to a "Mediterranean diet" was associated with a 40% increase in the probability of pregnancy. PMID: 20189169
Walthes DC, Abayasekara DRE, Aitken JR. Polyunsaturated fatty acids in male and female reproduction. Biology of reproduction 2007;77:190-201.
This is a very thorough review of what is known and not yet understood regarding the role of polyunsaturated fats like omega-3’s in male and female reproduction. The senior author is the leading authority on the role of oxidation products in impairing sperm function. Omega-3’s may be important in sperm production (Chavarro, 2009). PMID: 17442851
Wise LA, Cramer DW, Hornstein MD, Ashby RK, Missmer SA. Physical activity and semen quality among men attending an infertility clinic. Fertil Steril 2011;95:1025-30.
Men biking > or = 5 hours per week had reduced fertility and total motile sperm. It is difficult to separate vigorous activity from heating of the testicles with biking. PMID: 21122845
Wise LA, Rothman KJ, Mikkelsen EM, Sorensen HT, Riis AH, Hatch EE. A prospective cohort study of physical activity and time to pregnancy. Fertil Steril 2012;97:1136-42.
This study in women showed reduced fertility with > or = 5 hours of vigorous activity per week. The was no such adverse effect in obese women. PMID: 22425198
Wright DL, Smith KW, Ehrlich S, Berry K. Maternal hair mercury levels and early in vitro fertilization (IVF) outcomes. Fertil Steril 2011;96, suppl:S7.
Hair mercury levels were very strongly correlated with total fish intake. Higher levels correlated with embryo implantation.
Zitzmann M, Rolf C, Nordhoff V, Schrader G, Rickert-Fohring M, Gassner P, et al. Male smokers have a decreased success rate for in vitro fertilization and intracytoplasmic sperm injection. Fertil Steril 2003;79:1550-4.
In a study of 301 couples having IVF, pregnancy rates for male smokers were reduced with ICSI (22%) and IVF (18%) compared to non-smokers (38% and 32%). This study indicated that ICSI does not make up for the adverse effect of smoking, probably because smoking increases sperm DNA fragmentation. Males who smoke should take high doses of antioxidants for at least two months prior to IVF or ICSI (Greco, 2005). PMID: 12801558