Research - Infertility
Some sunscreen ingredients may disrupt sperm cell function
Many ultraviolet (UV)-filtering chemicals commonly used in sunscreens interfere with the function of human sperm cells, and some mimic the effect of the female hormone progesterone, a new study finds. Results of the Danish study will be presented Friday at the Endocrine Society's 98th annual meeting in Boston.
"These results are of concern and might explain in part why unexplained infertility is so prevalent," said the study's senior investigator, Niels Skakkebaek, MD, DMSc, a professor at the University of Copenhagen and a researcher at the Copenhagen University Hospital, Rigshospitalet.
Although the purpose of the chemical UV filters is to reduce the amount of the sun's UV rays getting through the skin by absorbing UV, some UV filters are rapidly absorbed through the skin, Skakkebaek said. UV filter chemicals reportedly have been found in human blood samples and in 95 percent of urine samples in the U.S., Denmark and other countries.
Skakkebaek and his colleagues tested 29 of the 31 UV filters allowed in sunscreens in the U.S. or the European Union (EU) on live, healthy human sperm cells, from fresh semen samples obtained from several healthy donors. The sperm cells underwent testing in a buffer solution that resembled the conditions in female fallopian tubes.
Specifically, the investigators evaluated calcium signaling, which is signaling inside the cell brought on by changes in the concentration of calcium ions. Movement of calcium ions within sperm cells, through calcium ion channels, plays a major role on sperm cell function, according to Skakkebaek. CatSper is a sperm-specific calcium ion channel that he said is essential for male fertility. This channel is the main sperm receptor for progesterone, a potent hormone attractant for human sperm cells. Binding of progesterone to CatSper causes a temporary influx, or surge, of calcium ions into the sperm cell, controlling several sperm functions necessary for fertilization.
The researchers found that 13, or 45 percent, of the 29 UV filters tested induced calcium ion influxes in the sperm cells, thus interfering with normal sperm cell function. "This effect began at very low doses of the chemicals, below the levels of some UV filters found in people after whole-body application of sunscreens," Skakkebaek said.
Furthermore, nine of the 13 UV filters seem to induce this calcium ion influx by directly activating the CatSper channel, thereby mimicking the effect of progesterone. This finding suggests that these UV filters are endocrine disruptors, Skakkebaek said. In addition, several of the UV filters affected important sperm functions normally controlled via CatSper, such as sperm motility.
Skakkebaek called for clinical studies to investigate whether chemical UV filters affect human fertility. He added, "Our study suggests that regulatory agencies should have a closer look at the effects of UV filters on fertility before approval."
Eight of the 13 UV filters that disrupted sperm cell function are approved for use in the U.S. They are avobenzone, homosalate, meradimate, octisalate (also known as octyl salicylate), octinoxate (or octyl methoxycinnamate), octocrylene, oxybenzone (also called benzophenone-3 or BP-3) and padimate O. These chemicals are common active ingredients in sunscreens as well as sunscreen-containing personal care products, such as makeup, moisturizers and lip balms.
PhD student and coauthor Anders Rehfeld, MD, will present the study findings
Source : Science Daily
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Effects of Common Fig (Ficus carica) Leaf Extracts on Sperm Parameters and Testis of Mice Intoxicated with Formaldehyde
Majid Naghdi, 1 Maryam Maghbool, 2 Morteza Seifalah-Zade, 3 Maryam Mahaldashtian, 1 Zohreh Makoolati, 1 , * Seyed Amin Kouhpayeh, 4 Afsaneh Ghasemi, 5 and Narges Fereydouni 1
Formaldehyde (FA) is the leading cause of cellular injury and oxidative damage in testis that is one of the main infertility causes. There has been an increasing evidence of herbal remedies use in male infertility treatment. This assay examines the role of Ficus carica (Fc) leaf extracts in sperm parameters and testis of mice intoxicated with FA. Twenty-five adult male mice were randomly divided into control; sham; FA-treated (10 mg/kg twice per day); Fc-treated (200 mg/kg); and FA + Fc-treated groups. Cauda epididymal spermatozoa were analyzed for viability, count, and motility. Testes were weighed and gonadosomatic index (GSI) was calculated. Also, histoarchitecture of seminiferous tubules was assessed in the Haematoxylin and Eosin stained paraffin sections. The findings showed that FA significantly decreased GSI and increased percentage of immotile sperm compared with control group. Disorganized and vacuolated seminiferous epithelium, spermatogenic arrest, and lumen filled with immature germ cells were also observed in the testes. However, Fc leaf extracts improved sperm count, nonprogressive motility of spermatozoa, and GSI in FA-treated testes. Moreover, seminiferous tubule with spermatogenic arrest was rarely seen, indicating that Fc has the positive effects on testis and epididymal sperm parameters exposed with FA.
Source : Evidence Based Complementary and Alternative Medicine
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Greene Guide: Functional Fertility Foods
There are few topics as emotionally driven as food choices. For most of us, our dietary choices are guided mostly by our taste preferences, familiarity (think comfort foods), and convenience. In fact, much of what passes as nutritional science in the popular media is incorrect or overstated. As a result, there are often widely held misconceptions and untruths about what is a "healthy food."
A classic example is soy-based food products. About 4 years ago, I wrote a column to debunk the popular (and inaccurate) belief that some of the hormone-like chemicals -- called phytoestrogens -- in these healthy beans could interfere with fertility. The latest research goes one step further suggesting that these foods actually boost the pregnancy rates in women undergoing advanced reproductive techniques (ART).
It's been well established that adding soy based foods can lead to small changes in thehormone balance of people that eat them. But for too long, people who wanted to promote unhealthy dietary choices successfully created concerns among fertility patients. Then two clinical studies came along that demonstrated that women taking soy supplements during either ovulation induction treatment or IVF cycles had higher pregnancy rates.
But the problem with these studies was that the supplements that were used boosted the level of phytoestrogens to levels that are more than 10 times higher than those of people eating a traditional Asian diet. New research has provided more practical insights into the health benefits achieved by simply switching to easily obtained soy based foods.
This latest study was very practical because researchers looked at the dietary choices in a group of 315 women that ultimately completed 520 ART cycles in 2013. Better still, they followed them prospectively to minimize the risk of obtaining biased results. They then looked at various results from their IVF cycles.
They found that the eggs from women that were eating foods that contained soy had a higher fertilization rate. More specifically, they found that the clinical pregnancy rate was 11% higher and live birth rate was 13% higher for the soy group after they were age-matched with women who did not eat soy. In fact, women who were consuming the most amount of soy had a nearly 80% higher chance of success.
The bottom line was that soy containing foods seem to be very beneficial to women undergoing fertility treatment, without making huge dietary changes.
An important step towards validating any finding is to then try to establish a theory of how the intervention may have resulted in the finding. The previous studies on soy supplements and IVF outcome suggested that the isoflavones -- these are the estrogen-like chemicals in soybeans -- resulted in a healthier uterine lining and thereby improved the ability of embryos to implant. They based this assumption on the fact that the ultrasound imaging of the lining appeared different.
This recent study did not find any such changes. Instead, they hypothesized that the benefits are demonstrated by the fertilization rate of the eggs from the women eating soy versus those who weren't eating soy. The fact that it was higher in the soy group suggests that eating soy may improve egg quality. Regardless of the mechanism, all of the research agrees that dietary soy is associated with higher pregnancy rates and a greater chance at a live birth.
Maybe the most important aspect of clinical research is guiding and motivating patients on how and when to implement changes. Given the large number of products that now contain soy as well as the various "meat substitutes" (e.g., veggie patties, soy milk, soy butter, soy yogurt) it makes sense to encourage women going through IVF to try to make some conscious changes to select these products or to eat soybeans.
Another potential advantage of reducing meat, chicken, and fish consumption is that plant-based proteins contain far less of the unhealthy aspects of our modern diet, like hormone disrupting chemicals, pesticides, and antibiotics. The end result is not only a higher chance of conceiving but also of having a healthier pregnancy and giving your child the very best start possible.
Robert Greene, MD, is a reproductive endocrinologist with Conceptions Reproductive Associates in Denver.
Source : Medpage
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Toiletry chemicals linked to testicular cancer and male infertility cost EU millions, report says
Nordic Council calls on EU to ban damaging compounds found in household products that cost millions due to their harmful impact on male reproductive health
The hormone-mimicking chemicals used routinely in toiletries, cosmetics, medicines, plastics and pesticides cause hundreds of millions of euros of damage to EU citizens every year, according to the first estimate of their economic impact.
The endocrine disruptor compounds (EDCs) are thought to be particularly harmful to male reproductive health and can cause testicular cancer, infertility, deformation of the penis and undescended testicles.
The new report, from the Nordic Council of Ministers, focuses on the costs of these on health and the ability to work but warns that they “only represent a fraction of the endocrine-related diseases” and does not consider damage to wildlife. Another new study, published in a medical journal, showed an EDC found in anti-perspirants reduced male fertility by 30%.
The Nordic Council, representing the governments of governments of Denmark, Finland, Iceland, Norway and Sweden, is demanding the European Union speeds up its plan to identify, assess and ban harmful EDCs. Sweden is already taking legal action against the EU over its missed deadlines, which it blamed on lobbying by the European chemical industry.
“I am not happy that taxpayers have to pay for the damage caused by EDCs, while industry saves money by not investigating their chemicals properly,” said Danish environment minister Kirsten Brosbøl on publication of the new report.
Michael Warhurst, of campaign group Chem Trust, said: “Companies should focus on developing and producing products that don’t contain hormone disruptors and other problem chemicals. This will give them a competitive advantage as controls on these chemicals become stricter around the world – and as consumers become more aware of this issue.”
The report, called The Cost of Inaction, uses the extensive health records collected by the Nordic countries to determine the incidence of the male reproductive health problems linked to EDCs and then uses Swedish data to estimate costs. These are extrapolated to the population of the EU’s 28 nations.
The report also assesses the proportion of the health problems attributable to EDCs, with a central estimate of 20%, leading to a conclusion that the male reproductive health problems cost the EU €592m (£470m) a year. The report states: “Minimising exposure to endocrine disruptors will not only remove distress and pain for the persons (and the wildlife) affected, it will also save the society from considerable economic costs.”
The EU, which would be the first authority in the world to regulate EDCs, is currently conducting a public consultation on a scientific method to identify the chemicals, which ends on 16 January. In 2011, the UK and German governments lobbied to EU to restrict the definition of EDCs to only the most potent chemicals, a proposal described as a “loophole” by critics.
Peter Smith, executive director for product stewardship at CEFIC, which represents the European chemical industry, said the Nordic report attribution of health problems to EDCs was “arbitrary”. He said: “The link between exposure to a chemical and an illness has not been shown in many cases. The authors themselves say they have some trouble with causality.”
Smith said the delays to EDC regulation in the EU did not suit the industry. “Nobody is happy with the delays. But we would prefer it to be permanent and right rather than temporary and wrong.” He said case-by-case rigorous assessment was needed and that any precautionary action had to be proportional to the evidence of harm.
However, Professor Andreas Kortenkamp, a human toxicologist at Brunel University London in the UK, said the epidemiological work needed to prove causation is very difficult. For example, he said, analysing links to birth defects would having taken tissue samples from mothers before they gave birth.
“Hard evidence for effects in humans is difficult to demonstrate, though there are some exceptions,” he said. “But there is very good, strong evidence from animal and cell line test systems. The chemical industry only likes to emphasis the first part of that.” He said precaution was the only safe approach and said the Nordic report was good work.
“Industry lobbying has put regulation back by 3-5 years, which was entirely the intention,” said Kortenkamp, who led a 2012 review of EDCs for the EU which found new regulations were needed. “Every year of no regulation means millions of euros to the industry. That is what it is all about.”
In 2012, the World Health Organiation and the UN environment programme published a major report on the state of EDC science, which concluded that communities across the globe were being exposed to EDCs and their associated risks and that urgent research on the health and environmental impacts was needed. Dr Maria Neira, the WHO’s director for public health and environment said at the time: “We all have a responsibility to protect future generations.” Another review in 2012 by the European Environment Agency advised “a precautionary approach to many of these chemicals until their effects are more fully understood.”
Source : The Guardian
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Comparison on the Effects and Safety of Tualang Honey and Tribestan in Sperm Parameters, Erectile Function, and Hormonal Profiles among Oligospermic Males
Shaiful Bahari Ismail,1 Mohd. Bustamanizan Bakar,1 Nik Hazlina Nik Hussain,1 Mohd Noor Norhayati,1 Siti Amrah Sulaiman,1 Hasnan Jaafar,1 Samsul Draman,2 Roszaman Ramli,2 and Wan Zahanim Wan Yusoff3
1School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia
2International Islamic University, Bandar Indera Mahkota, 25200 Kuantan, Pahang, Malaysia
3Hospital Raja Perempuan Zainab II, 15200 Kota Bharu, Kelantan, Malaysia
Introduction. This study aims to evaluate the effectiveness of Tualang honey on sperm parameters, erectile function, and hormonal and safety profiles.
Methodology. A randomized control trial was done using Tualang honey (20 grams) and Tribestan (750 mg) over a period of 12 weeks. Sperm parameters including sperm concentration, motility, and morphology were analyzed and erectile function was assessed using IIEF-5 questionnaire. Hormonal profiles of testosterone, FSH, and LH were studied. The volunteers were randomized into two groups and the outcomes were analyzed using SPSS version 18.
Results. A total of 66 participants were involved. A significant increment of mean sperm concentration (P<0.001), motility (P=0.015) and morphology (P=0.008) was seen in Tualang honey group. In Tribestan group, a significant increment of mean sperm concentration (P=0.007) , and morphology (P=0.009) was seen. No significant differences of sperm concentration, motility, and morphology were seen between Tualang honey and Tribestan group and similar results were also seen in erectile function and hormonal profile. All safety profiles were normal and no adverse event was reported.
Conclusion. Tualang honey effect among oligospermic males was comparable with Tribestan in improving sperm concentration, motility, and morphology. The usage of Tualang honey was also safe with no reported adverse event.
Source : Evidence Based Complementary and Alternative Medicine
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Use of laptop computers connected to internet through Wi-Fi decreases human sperm motility and increases sperm DNA fragmentation
Conrado Avendano, M.S., ~ a Ariela Mata, M.S.,a Cesar A. Sanchez Sarmiento, M.D., Ph.D., a and Gustavo F. Doncel, M.D., Ph.D.b
a Nascentis Medicina Reproductiva, Cordoba, Argentina; and b CONRAD, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, Virginia
Objective: To evaluate the effects of laptop computers connected to local area networks wirelessly (Wi-Fi) on human spermatozoa.
Design: Prospective in vitro study.
Setting: Center for reproductive medicine.
Patient(s): Semen samples from 29 healthy donors.
Intervention(s): Motile sperm were selected by swim up. Each sperm suspension was divided into two aliquots. One sperm aliquot (experimental) from each patient was exposed to an internet-connected laptop by Wi-Fi for 4 hours, whereas the second aliquot (unexposed) was used as control, incubated under identical conditions without being exposed to the laptop.
Main Outcome Measure(s): Evaluation of sperm motility, viability, and DNA fragmentation.
Result(s): Donor sperm samples, mostly normozoospermic, exposed ex vivo during 4 hours to a wireless internet-connected laptop showed a significant decrease in progressive sperm motility and an increase in sperm DNA fragmentation. Levels of dead sperm showed no significant differences between the two groups.
Conclusion(s): To our knowledge, this is the first study to evaluate the direct impact of laptop use on human spermatozoa. Ex vivo exposure of human spermatozoa to a wireless internet-connected laptop decreased motility and induced DNA fragmentation by a nonthermal effect. We speculate that keeping a laptop connected wirelessly to the internet on the lap near the testes may result in decreased male fertility. Further in vitro and in vivo studies are needed to prove this contention.
Source : Journal Fertility and Sterility
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Effect of mobile telephones on sperm quality: A systematic review and meta-analysis
Mobile phones are owned by most of the adult population worldwide. Radio-frequency electromagnetic radiation (RF-EMR) from these devices could potentially affect sperm development and function. Around 14% of couples in high- and middle-income countries have difficulty conceiving, and there are unexplained declines in semen quality reported in several countries. Given the ubiquity of mobile phone use, the potential role of this environmental exposure needs to be clarified. A systematic review was therefore conducted, followed by meta-analysis using random effects models, to determine whether exposure to RF-EMR emitted from mobile phones affects human sperm quality. Participants were from fertility clinic and research centres. The sperm quality outcome measures were motility, viability and concentration, which are the parameters most frequently used in clinical settings to assess fertility.
We used ten studies in the meta-analysis, including 1492 samples. Exposure to mobile phones was associated with reduced sperm motility (mean difference − 8.1% (95% CI − 13.1, − 3.2)) and viability (mean difference − 9.1% (95% CI − 18.4, 0.2)), but the effects on concentration were more equivocal. The results were consistent across experimental in vitro and observational in vivo studies. We conclude that pooled results from in vitro and in vivo studies suggest that mobile phone exposure negatively affects sperm quality. Further study is required to determine the full clinical implications for both sub-fertile men and the general population.
Source : Environmental International
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Effects of the Czech Propolis on Sperm Mitochondrial Function
Miroslava Cedikova,1,2 Michaela Miklikova,1,2 Lenka Stachova,3 Martina Grundmanova,4 Zdenek Tuma,2,5 Vaclav Vetvicka,6 Nicolas Zech,7 Milena Kralickova,1,2 and Jitka Kuncova2,4
1Department of Histology and Embryology, Faculty of Medicine in Pilsen, Charles University in Prague, 301 00 Pilsen, Czech Republic
2Biomedical Centre, Faculty of Medicine in Pilsen, Charles University in Prague, 301 00 Pilsen, Czech Republic
3Institute of Pharmacology and Toxicology, Faculty of Medicine in Pilsen, Charles University in Prague, 301 00 Pilsen, Czech Republic
4Department of Physiology, Faculty of Medicine in Pilsen, Charles University in Prague, 301 00 Pilsen, Czech Republic
51st Internal Department, Faculty of Medicine and Teaching Hospital in Pilsen, Charles University in Prague, 301 00 Pilsen, Czech Republic
6Department of Pathology, University of Louisville, Louisville, KY 40292, USA
7IVF Centers Prof. Zech - Pilsen, 301 00 Pilsen, Czech Republic
Propolis is a natural product that honeybees collect from various plants. It is known for its beneficial pharmacological effects. The aim of our study was to evaluate the impact of propolis on human sperm motility, mitochondrial respiratory activity, and membrane potential. Semen samples from 10 normozoospermic donors were processed according to the World Health Organization criteria. Propolis effects on the sperm motility and mitochondrial activity parameters were tested in the fresh ejaculate and purified spermatozoa. Propolis preserved progressive motility of spermatozoa in the native semen samples. Oxygen consumption determined in purified permeabilized spermatozoa by high-resolution respirometry in the presence of adenosine diphosphate and substrates of complex I and complex II (state OXPHOS I + II) was significantly increased in the propolis-treated samples. Propolis also increased uncoupled respiration in the presence of rotenone (state ETS II) ) and complex IV activity, but it did not influence state LEAK induced by oligomycin. Mitochondrial membrane potential was not affected by propolis. This study demonstrates that propolis maintains sperm motility in the native ejaculates and increases activities of mitochondrial respiratory complexes II and IV without affecting mitochondrial membrane potential. The data suggest that propolis improves the total mitochondrial respiratory efficiency in the human spermatozoa in vitro thereby having potential to improve sperm motility.
Source : Evidence Based Complementary and alternative Medicine
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Beneficial Effects of Ashwagandha Root in the Treatment of Male Infertility
by Shari Henson
Reviewed: Gupta A, Mahdi AA, Shukla KK, et al. Efficacy of Withania somnifera on seminal plasma metabolites of infertile males: a proton NMR study at 800 MHz. J Ethnopharmacol. 2013;149(1):208-214.
Infertility affects between 10 to 15% of couples worldwide.1 In traditional Indian systems of medicine, ashwagandha (Withania somnifera, Solanaceae) root is a highly regarded tonic and adaptogenic herb, and it also is used to treat impotence and infertility. There is some experimental evidence that ashwagandha root improves semen quality and decreases spermatorrhea by regulating reproductive hormone levels and oxidative stress.2,3 This study evaluated the effects of ashwagandha root powder on seminal plasma metabolites, enzymes, and hormones in infertile men by using high-resolution proton nuclear magnetic resonance (NMR) spectroscopy.
Ashwagandha root contains withanosides, essential and non-essential fatty acids, amino acids, sterols, catecholamines, aromatic alcohols and acids, gamma-aminobutyric acid, and glycerol. The roots for this study (obtained from the Central Council for Research in Unani Medicine; New Delhi, India) were dried and ground into a fine powder.
One hundred and eighty infertile male subjects aged 22 to 45 years recruited from the infertility clinic at King George’s Medical University in Lucknow, India — plus an additional 50 healthy, age-matched men — were included in the study and subdivided into the following groups (experimental subjects: n=180; control subjects: n=50):
Normozoospermic (NZ; n=60) men who had a normal semen profile (>20 x 106 spermatozoa/mL, >40% motility, and >40% normal morphology) and infertility of unknown etiology;
Oligozoospermic (OZ; n=60) men who had a sperm concentration <20 x 106/mL, >40% motility, and >40% normal morphology;
Asthenozoospermic (AZ; n=60) men who had a sperm concentration >20 x 106/mL, but <40% motility, and >40% normal morphology; and
An additional 50 healthy, age-matched men (>20 x 106 spermatozoa/mL, >40% motility, and >40% normal morphology) who served as controls (CZ; n=50).
The subjects in the NZ, OZ, and AZ groups were prescribed ashwagandha root powder (five grams daily taken orally with milk in a single dose; qualitative analysis of the roots not provided) for three months. Semen and blood samples were collected at baseline and after three months of treatment.
Seminal plasma samples were analyzed using proton NMR spectroscopy to determine concentrations of the metabolites lactate, alanine, glutamate, glutamine, citrate, lysine, choline, glycerophosphocholine (GPC), glycine, tyrosine, histidine, phenylalanine, and uridine. Sperm concentration, motility, lipid peroxide (LPO), enzyme, and hormone levels also were measured.
The concentrations of lysine, choline, glutamine, glycine, tyrosine, and uridine did not change significantly in any group post-treatment. Compared with baseline values, alanine, glutamate, citrate, GPC, and histidine increased significantly in the NZ, OZ, and AZ groups after three months of treatment. Phenylalanine concentrations decreased significantly compared with baseline values in NZ and OZ groups, while lactate concentrations showed significant differences compared with baseline values in OZ and AZ groups. Sperm concentration, motility, and LPO levels also improved significantly in these groups compared with baseline values.
According to the authors, this is the first study to analyze metabolite concentrations using an 800 MHz NMR spectrometer to measure levels of the enzymes alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase (LDH), and isocitrate dehydrogenase in the seminal plasma of infertile males in an attempt to elucidate the physiological effects of ashwagandha. Enzyme levels increased significantly in all groups of infertile subjects post-treatment compared with baseline, except for LDH in the NZ group.
Compared with baseline, there was a significant increase in luteinizing hormone and testosterone in all groups post-treatment. Follicle-stimulating hormone and prolactin levels decreased in all three groups of infertile subjects but were significant only in OZ and AZ groups.
The authors note that “[a]berrations of endogenous metabolites, enzymatic activities, and hormone levels commonly precede the onset of infertility.” An important finding in this study is that oral intake of ashwagandha for three months by infertile men resulted in substantial enhancement of seminal plasma metabolic profiles and improvements in enzymatic, hormonal, and clinical parameters (sperm concentration, motility, and LPO). The authors conclude that ashwagandha “can be used as an alternative empirical therapy for the treatment and clinical management of male infertility.”
However, this study could have benefitted from the inclusion of a placebo group, randomization, and both baseline and endpoint measurements of control group blood and semen values (the authors procured and evaluated only one blood and semen sample for each control group member during the study). Also, the authors could have provided demographic information of the subjects involved in the study.
1. Callister LC. Global infertility: are we caring yet? MCN Am J Matern Child Nurs. 2010;35(3):174.
2. Mahdi AA, Shukla KK, Ahmad MK, et al. Withania somnifera improves semen quality in stress-related male fertility. Evid Based Complement Alternat Med. 2011;2011:576962. doi: 10.1093/ecam/nep138.
3. Ahmad MK, Mahdi AA, Shukla KK, et al. Withania somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress in seminal plasma of infertile males. Fertil Steril. 2010;94(3):989-996.
Source : Herbal Gram - American Botanical Council
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Can Chinese Herbal Medicine Improve Outcomes of In Vitro Fertilization? A Systematic Review and Meta-Analysis of Randomized Controlled Trials
- Huijuan Cao,
- Mei Han,
- Ernest H. Y. Ng,
- Xiaoke Wu,
- Andrew Flower,
- George Lewith,
- Jian-Ping Liu
Background A large number of infertile couples are choosing Chinese herbal medicine (CHM) as an adjuvant therapy to improve their success when undergoing in vitro fertilization (IVF). There is no systematic review to evaluate the impact of CHM on the IVF outcomes.
Objective To evaluate the effectiveness of CHM with concurrent IVF versus IVF alone on the outcomes of IVF and its safety.
Methods The protocol of this study is registered at PROSPERO. Eligible RCTs searched from 8 databases which compared a combination of CHM and IVF with IVF alone were included. Two authors independently selected studies, extracted data and assessed methodological quality. Meta-analysis of RCTs was conducted if there was non-significant heterogeneity (evaluated by I2 test) among trials. All statistical analysis was performed using RevMan 5.1 software.
Results Twenty trials involving 1721 women were included in the meta-analysis. Three trials were evaluated as having an unclear risk of bias. The remaining trials were evaluated as having a high risk of bias. Combination of CHM and IVF significantly increases clinical pregnancy rates (OR 2.04, 95%CI 1.67 to 2.49, p<0.00001) and ongoing pregnancy rates (OR 1.91, 95%CI 1.17 to 3.10, p = 0.009). Use of CHM after embryo transfer had no better outcome in reducing the rate of ovarian hyper stimulation syndrome (OR 0.39, 95%CI 0.14 to 1.11, p = 0.08).
Conclusions This meta-analysis showed that combination of IVF and CHM used in the included trials improve IVF success, however due to the high risk of bias observed with the trials, the significant differences found with the meta-analysis are unlikely to be accurate. No conclusion could be drawn with respect to the reproductive toxicity of CHM. Further large randomized placebo controlled trials are warranted to confirm these findings before recommending women to take CHM to improve their IVF success.
Source : PLOS One
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Clinical Evaluation of the Spermatogenic Activity of the Root Extract of Ashwagandha (Withania somnifera) in Oligospermic Males: A Pilot Study
Vijay R. Ambiye,1 Deepak Langade,2 Swati Dongre,3 Pradnya Aptikar,4 Madhura Kulkarni,5 and Atul Dongre3
1Mahalaxmi Clinic, Nanaddham, Sulochana Shetty Marg, Sion (E), Mumbai, Maharashtra 400022, India
2Department of Pharmacology, B.V.D.U. Dental College & Hospital, Sector-7, C.B.D., Belpada, Navi Mumbai, Maharashtra 400614, India
3Trupti Hospital & Santati Fertility Center, Thane, Maharashtra 400607, India
4Arya Clinic, Thane, Maharashtra 400601, India
5Arogyadham, Manpada, Thane, Maharashtra 400607, India
Ashwagandha (Withania somnifera) has been described in traditional Indian Ayurvedic medicine as an aphrodisiac that can be used to treat male sexual dysfunction and infertility. This pilot study was conducted to evaluate the spermatogenic activity of Ashwagandha root extract in oligospermic patients. Forty-six male patients with oligospermia (sperm count < 20 million/mL semen) were enrolled and randomized either to treatment (n=21) with a full-spectrum root extract of Ashwagandha (675 mg/d in three doses for 90 days) or to placebo (n=25) in the same protocol. Semen parameters and serum hormone levels were estimated at the end of 90-day treatment. There was a 167% increase in sperm count (9.59 ± 4.37 × 106/mL to 25.61 ± 8.6 × 106/mL; P<0.0001), 53% increase in semen volume (1.74 ± 0.58 mL to 2.76 ± 0.60 mL; P<0.0001), and 57% increase in sperm motility (18.62 ± 6.11% to 29.19 ± 6.31%; P<0.0001) on day 90 from baseline. The improvement in these parameters was minimal in the placebo-treated group. Furthermore, a significantly greater improvement and regulation were observed in serum hormone levels with the Ashwagandha treatment as compared to the placebo. The present study adds to the evidence on the therapeutic value of Ashwagandha (Withania somnifera), as attributed in Ayurveda for the treatment of oligospermia leading to infertility.
Source : Evidence Based Complementary and Alternative Medicine
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Chemicals Tied to Reduced Fertility in IVF
Phthalates, chemicals found in plastics, fragrances, and cosmetics, may affect the chances of successful in vitro fertilization, researchers reported.
In a prospective cohort study, urinary metabolite levels of the phthalates in the family of di-2-ethylhexyl-P (DEHP) were associated with significantly increased risks of implantation failure across increasing quartiles of the metabolite (P=0.031 for trend), according to Irene Souter, MD, of Massachusetts General Hospital, and colleagues.
They presented their findings at the European Society of Human Reproduction and Embryology meeting in London.
"Our data support the hypothesis that exposure to specific phthalates might lead to adverse female reproductive outcomes," Souter said in a statement.
Phthalates are used in a host of plastics, including PVC and vinyl, to soften them, and in personal care products and aerosols with fragrances in them. These products are ubiquitous in the environment and studies have shown them to be linked with reproductive issues in men, since they have been known to mimic the hormone testosterone.
But the effects of phthalates are less well-studied in women, particularly with regard to reproductive health.
Specifically, Souter and colleagues questioned whether phthalates had an impact on various factors among women having IVF, such as ovarian response, oocyte yield, embryonic development and implantation failure.
They followed 231 women ages 18 to 45 who'd had a total of 325 fresh treatment cycles at Massachusetts General Hospital Fertility Center between 2004 and 2012.
The researchers took urine samples at the start of treatment and either at the early/mid-follicular phase or at oocyte retrieval. They looked for urinary metabolites of several phthalates, including mono(2-ethylhexyl)-P (MEHP), monobutyl-P (MBP), and the sum of di-2-ethylhexyl-P phthalates (sum-DEHP).
They also assessed various markers of response to IVF, including serum peak estradiol, implantation failure, and the number of retrieved, mature, and fertilized oocytes.
Overall, the researchers detected urinary phthalates in more than 95% of the samples.
They found significant increased risks of implantation failure across increasing quartiles of sum-DEHP levels (P=0.031):
- Q2 -- OR 1.41
- Q3 -- OR 1.76
- Q4 -- OR 2.05
- Q2 -- 1.96
- Q3 -- 2.02
- Q4 -- 1.85
They reported a similar trend with increasing sum-DEHP quartiles, although it was not significant (9.09%, 9.46%, 10.2%, P=0.074).
There was also a decrease in the number of mature oocytes with increasing MEHP quartiles (P=0.016) and sum-DEHP metabolites (P=0.018).
However, there were no associations between urinary phthalate metabolites and peak estradiol, rates of fertilization, or embryonic cleavage, they reported.
They cautioned that the study was limited because it precluded assessment of long-term exposure to phthalates, and because the results may not be generalizable to women who are conceiving naturally.
Still, Souter and colleagues concluded that their results support the hypothesis that phthalates may have an adverse effect on female fertility, particularly when it comes to IVF
Source : MedPage Today
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Influence of acupuncture on the outcomes of in vitro fertilisation when embryo implantation has failed: a prospective randomised controlled clinical trial
Abstract OBJECTIVE: To evaluate the effectiveness of acupuncture and moxibustion as an adjuvant treatment in women undergoing in vitro fertilisation (IVF) when embryo implantation has failed.
METHODS: A prospective, randomised controlled clinical trial was conducted with 84 infertile patients who had had at least two unsuccessful attempts of IVF. The patients were randomised in three groups: control (n=28), sham (n=28) and acupuncture (n=28). The sample size was calculated by assuming a pregnancy rate of 10% when embryo implantation had failed. The pregnancy rates of the current IVF cycle were evaluated by measurement of blood β human chorionic gonadotrophin (βhCG) and subsequent transvaginal ultrasound. Acupuncture was performed on the first and seventh day of ovulation induction, on the day before ovarian puncture and on the day after embryo transfer. In the acupuncture group, patients were treated with moxibustion at nine acupuncture points (BL18, BL22, BL23, BL52, CV3, CV4, CV5, CV7, GV4) and needling at 12 points. In the sham group needles were inserted in eight areas that did not correspond to known acupuncture points.
RESULTS: The clinical pregnancy rate in the acupuncture group was significantly higher than that in the control and sham groups (35.7% vs 7.1% vs 10.7%; p=0.0169).
CONCLUSIONS: In this study, acupuncture and moxibustion increased pregnancy rates when used as an adjuvant treatment in women undergoing IVF, when embryo implantation had failed.
Source : Acupunct Med. 2013 Mar 19
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Low Sperm Count Tied to High TV Time
Today's couch potatoes could turn into tomorrow's reproductively challenged spuds, according to results of a study linking TV time to poorer sperm quality in young men.
Men who watched TV for 20 or more hours a week had a 44% lower sperm concentration compared with men who did not watch TV. In a multivariable analysis, sperm concentration tended to be inversely associated with time spent watching TV, and a trend toward lower sperm count emerged from the data.
The study also revealed significant positive association between physical activity and sperm quality, which has a controversial research history, investigators reported online in the British Journal of Sports Medicine.
"Men who engaged in the most moderate to vigorous physical activity and those who watched the least TV had the highest sperm counts," Audrey J. Gaskins, a doctoral student at the Harvard School of Public Health, told MedPage Today. "Since we know very little about how lifestyle may impact semen quality and male fertility in general, the fact that we could identify two potentially modifiable factors that appear to have such a big impact on sperm count is quite exciting."
Several studies have documented a decline in semen quality over the past several decades, but other studies have not. More consistent evidence of declining quality has come from studies limited to Western populations, but the reasons for a decline remain unclear.
Over the same time frame, physical activity has decreased and sedentary behavior has increased, suggesting a possible adverse effect on sperm characteristics, in addition to sedentary lifestyles' documented associations with obesity, diabetes, and cardiovascular disease.
Sedentary behavior also has been associated with increased scrotal temperature, which may adversely affect sperm quality, although the data are inconsistent, the authors noted. Moreover, watching TV, one of the most common sedentary activities, remains unexplored as a potential risk to sperm quality.
On the other hand, intense physical activity (primarily long-distance running and cycling) has been associated with reduced sperm quality. In contrast, the relationship between moderate physical activity and semen quality has remained unexplored, the authors continued.
To address the unresolved issues, Gaskins and colleagues studied 222 male college students ages 18 to 22. Study participants reported their television viewing habits (TV, videos, and/or DVDs) and the estimated number of hours and intensity of physical activity engaged in for the previous 3 months.
The investigators assigned metabolic equivalent (MET) values to vigorous (MET >6), moderate (MET 3 to 6), and mild (MET <3) physical activities.
Participants could choose one of five categories of daily TV watching, ranging from none/almost none to >10 hours daily.
Each participant provided a semen specimen during a clinic visit, and the men were instructed to abstain from ejaculation for at least 48 hours before the visit.
Semen volume was estimated by a specimen's weight. Sperm concentration was determined by hemocytometry and motility by WHO 1999 criteria; sperm morphology by evaluation of Papanicolaou-stained slides.
The final analysis included 189 participants for whom there was complete data. Participants had a media age of 19.6, 81.5% were white, 58.4% had a normal body mass index (<25), and 77.4% were nonsmokers.
The median time spent in moderate or vigorous physical activity was 8.25 hours per week, and the median weekly TV time was 14 hours.
Assessments of semen quality showed a median sperm concentration of 53 x 106/mL, median proportion of progressively motile sperm of 60%, and median proportion of morphologically normal sperm of 8.5%.
Demographic variables did not have significant associations with physical activity or TV watching. Physically active men were more likely to have "prudent" dietary practices (defined as a diet high in fish, chicken, fruit, vegetables, legumes and whole grains), whereas increased TV time was associated with "Western" dietary practices (a diet high in red meat, butter, high-fat dairy and other fats, refined grains, pizza, snacks, energy drinks, and sweets). The difference was significant at (P<0.001).
Moderate-vigorous physical activity had a significant positive association with sperm concentration (P=0.003 for trend) and sperm count (P=0.04 for trend).
Sperm motility, sperm morphology, and sample volume had no associations with physical activity.
TV watching had an inverse association with sperm concentration, as men in the three lowest quartiles of TV watching had sperm concentrations 14% to 44% higher than those of men in the highest quartile (P=0.03 for trend).
A similar pattern was observed for the relationship between TV time and sperm count, resulting in a nonsignificant trend (P=0.06).
Time spent watching TV was not associated with sperm motility, sperm morphology, or sample volume.
Men who spent the most time watching TV and reported the least amount of physical activity had the lowest adjusted mean sperm concentration (24 x 106).
Physical activity and TV watching were not significantly correlated, suggesting independent effects on semen and sperm characteristics, said Gaskins.
The study findings are interesting but not sufficiently specific to draw conclusions, said Sheryl Kingsberg, PhD, of University Hospitals/Case Western Reserve University in Cleveland.
"What it says is that men in general need to pay attention to physical activity because it does potentially impact their fertility," Kingsberg told MedPage Today.
Whether TV watching has a cumulative effect on sperm quality over time is one of the unanswered questions raised by the study.
"We know that fertility goes down and sperm quality goes down with age. Whether that's correlated with the total number of hours they've spent watching television has yet to be determined," said Kingsberg.
"Walking to the refrigerator to get a beer does not count as physical activity," she added.
Source : MedPage Today
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Semen Quality and Sperm DNA Damage in Relation to Urinary Bisphenol A among Men from an Infertility Clinic
Bisphenol A (BPA) impairs spermatogenesis in animals, but human studies are lacking. We measured urinary BPA concentrations, semen quality, and sperm DNA damage (comet assay) in 190 men recruited through an infertility clinic. BPA was detected in 89% of samples, with a median (interquartile range [IQR]) concentration of 1.3 (0.8 – 2.5) ng/mL. Urinary BPA concentration was associated with slightly elevated, though not statistically significant, odds for below reference sperm concentration, motility, and morphology. When modeled as continuous dependent variables, an IQR increase in urinary BPA concentration was associated with declines in sperm concentration, motility, and morphology of 23% (95%CI –40%, -0.3%), 7.5% (-17%, +1.5%), and 13% (-26%, -0.1%), respectively, along with a 10% (0.03%, 19%) increase in sperm DNA damage measured as the percentage of DNA in comet tail. In conclusion, urinary BPA may be associated with declined semen quality and increased sperm DNA damage, but confirmatory studies are needed.
Source : Reprod Toxicol
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Walnuts May Improve Semen Quality
Healthy young men with a Western-style diet may be able to boost their sperm quality by eating a small packet of walnuts a day.
These are the findings of a new study that shows healthy American men in their 20s and 30s who ate a 75g (2.5 ozs) packet of walnuts a day were able to increase the vitality, motility and structure of their sperm compared to counterparts who did not eat walnuts.
A report on the study appeared online on 15 August in the Biology of Reproduction journal's papers-in-press section.
Infertility and subfertility is a common problem that affects about 70 million couples worldwide. Between a third and a half of cases are due to poor semen quality in the male partner, with scientists giving a number of reasons for this in industrialized societies: pollution, unhealthy lifestyles and the Western-style diet cited amongst them.
First author Wendie Robbins, of the University of California, Los Angeles (UCLA) and colleagues focused on the last of these, as they explained in their background information to the study:
"We tested the hypothesis that 75 gm of whole-shelled walnuts/day added to a Western-style diet of healthy young men would beneficially affect semen quality."
75 g is about 2.5 ozs, equivalent to one of those small snack-style packs you can get in the supermarket.
A small packet of walnuts a day appear to help improve the vitality of sperm Walnuts are rich in polyunsaturated fatty acids (PUFAs), which play an important role in maturing sperm and preserving the integrity of the membrane around the cell which in turn affects its ability to fertilize an egg.
In the Western-style diet, PUFAs are usually found in fish, fish oil supplements, flax seed and walnuts. Walnuts also offer an important source of linolenic acid (ALA), a natural plant source of omega-3.
For their study, which was partially funded by the California Walnut Commission, Robbins and colleagues enrolled 117 healthy men aged 21 to 35 who followed a Western-style diet.
The participants were randomly assigned to one of two groups: 58 were asked to avoid eating tree nuts, and 59 were asked to eat 75 g of walnuts a day.
The researchers picked 75 g because other studies have suggested this is enough to change lipid levels in the blood but not enough to make healthy young men put on weight.
All the participants gave blood and semen samples before and after the study period, which lasted 12 weeks.
The researchers assessed semen quality using the traditional measures of male fertility. These include sperm concentration, vitality (living versus dead sperm), motility (how well they travel towards an egg), morphology (shape and structure), and chromosome abnormalities.
The results found at the end of the 12 weeks, neither group showed significant changes in body weight, body mass, or physical activity levels (these factors can also affect sperm quality).
However, the men in the walnut group had higher levels of omega-6 and omega-3 (ALA) fatty acids in their blood at the end of the study period than they did at the start.
The men in the walnut group also experienced improvements in sperm quality over the 12 weeks of eating walnuts, there were significant increases in measures of vitality, motility, and morphology. Their sperm also showed fewer chromosome abnormalities at the end of the 12 weeks than it did at the start of the study.
The control group, however, showed no such changes.
The researchers conclude that their:
"Findings demonstrated that walnuts added to a Western-style diet improved sperm vitality, motility and morphology."
Note that the study only looks at the effect of walnut consumption on semen quality in healthy young men: it doesn't show whether it would have the same effect in men with fertility problems, or whether the observed improvements in semen quality actually result in increased fertility.
Source : Medical News Today
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BPA diminishes in vitro success.
Ehrlich, S, PL Williams, SA Missmer, JA Flaws, KF Berry, A Calafat, X Ye, JC Petrozza, D Wright and R Hauser. 2012.
Exposure to bisphenol A (BPA) at levels commonly found in the general population may cut a woman's chance of getting pregnant if she is undergoing fertility treatment, a study from Harvard University finds.Those with higher BPA levels were less likely to get pregnant than women with lower levels. The link was stronger in women having more intense fertility treatments. The pregnancies failed because the embryos did not attach to the uterus.
While animal studies show similar results, this is the first time researchers report a link in people. BPA is widely used in some plastics, most food can linings and certain receipt paper.
What did they do? Researchers followed 137 women seeking fertility treatment at Massachusetts General Hospital Fertility Center. They examined the relationship between BPA exposure and pregnancy success among women undergoing IVF treatment.
Women were of childbearing age (18-45 years), used their own eggs in the IVF procedure and most were Caucasian and non-smokers. They were followed through each IVF cycle until they delivered their baby or stopped treatment. The participants underwent one of three IVF treatment protocols based on whether they were "poor responders" or "good responders." Women who are “poor responders” require large doses of fertility drugs and end up with fewer eggs.
BPA concentrations in urine samples were measured at each fertility treatment. The researchers confirmed pregnancies – defined as successful embryo implantation – by measuring the levels in blood samples of a hormone produced during pregnancy – ß-human chorionic gonadotropin hormone (ß-HCG). The hormone is found in blood and urine of pregnant women as early as 10 days after conception.
Medical history, lifestyle factors, occupation and other personal information were collected in a nurse-administered questionnaire and/or in an in-depth take-home questionnaire.
Researchers categorized women into one of four exposure groups based on the BPA levels in their urine: 1.69 micrograms per liter (μg/L) or lower, 1.70-2.33 μg/L, 2.34-3.79 μg/L and 3.80 μg/L or higher. They compared the chances of getting pregnant in women in the highest exposure groups (1.70 μg/L and higher) to women in the lowest exposure group (1.69 μg/L or lower).
In their analysis, they considered several factors that could affect the association between BPA exposure and implantation failure, including women’s age, day of embryo transfer and specific IVF protocol treatment followed.
What did they find? Regardless of the factors considered, the results show a clear trend of increasing implantation failure with higher BPA levels. These effects were observed in women with BPA levels lower than those in women of childbearing age in the general U.S. population.
Average levels of BPA measured in the women's urine – 1.53 μg/L – were comparable to those reported in women from the general U.S. population – 1.97 μg/L.
Without taking into account women’s age, day of embryo transfer and IVF protocol followed, the chances of getting pregnant decreased with increasing exposure levels of BPA. Women in the highest exposure group had half the odds of getting pregnant than women with the lowest levels.
Findings were similar after controlling for women’s age, day of embryo transfer, and IVF protocol followed. The relationship was not as strong in women in the highest exposure group.
Researchers also observed stronger associations between BPA and failed pregnancies in women who were poor responders. Those with higher levels of BPA were less likely to become pregnant. Women who were poor responders were generally older and more likely to have past IVF treatment cycle failures. They also had reduced number of eggs, lower average number of eggs retrieved and diminished ovarian response to stimulation.
What does it mean? This is the first study to find an association between failed egg implantation and BPA exposure in women undergoing IVF treatment.
This finding is important because it provides the first human data on the association between implantation failure in women seeking IVF treatment and BPA exposure at levels observed in women of childbearing age in the general population. Results suggest that as BPA levels increase so do the number of failed pregnancies in women undergoing fertility treatment.
These findings confirm in people what has been observed in animal studies and support previous studies that link BPA to fertility problems in humans. Prior studies in humans report that BPA exposure is associated with recurrent miscarriages, quality and number of eggs retrieved during IVF treatment and peak hormone levels essential for a successful pregnancy.
Additionally, findings support earlier studies that suggest women seeking IVF treatment minimize their exposure to BPA (Fujimoto et al. 2011; Mol-Lin et al. 2010).
The results may not be applicable to women trying to conceive naturally. According to the authors, it is possible that women undergoing fertility treatment are more sensitive to BPA exposure due to different factors “including their underlying infertility, the in vitro conditions of early embryonic development or the ovarian hyperstimulation protocols.”
Nonetheless, because 10-15 percent of the population in the United States and developed countries are infertile, the results are still relevant to a large subset of the general population.
Source : Environmental Health News
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Withania somnifera Improves Semen Quality in Stress-Related Male Fertility
Abbas Ali Mahdi,1 Kamla Kant Shukla,1 Mohammad Kaleem Ahmad,1 Singh Rajender,2 Satya Narain Shankhwar,3 Vishwajeet Singh,3 and Deepansh Dalela1
1Department of Biochemistry, C.S.M. Medical University, Lucknow 26003, India
2Endrocrinology Division, Central Drug Research Institute, Lucknow 226001, India
3Department of Urology, C.S.M. Medical University, Lucknow 226003, India
Withania Somnifera also know as Ashwagandha
Stress has been reported to be a causative factor for male infertility. Withania somnifera has been documented in Ayurveda and Unani medicine system for its stress-combating properties. However, limited scientific literature is available on this aspect of W. somnifera. We undertook the present study to understand the role of stress in male infertility, and to test the ability of W. somnifera to combat stress and treat male infertility. We selected normozoospermic but infertile individuals (N = 60), further categorized in three groups: normozoospermic heavy smokers (N = 20), normozoospermics under psychological stress (N = 20) and normozoospermics with infertility of unknown etiology (N = 20). Normozoospermic fertile men (N = 60) were recruited as controls. The subjects were given root powder of W. somnifera at a rate of 5 g/day for 3 months. Measuring various biochemical and stress parameters before and after treatment, suggested a definite role of stress in male infertility and the ability of W. somnifera to treat stress-related infertility. Treatment resulted in a decrease in stress, improved the level of anti-oxidants and improved overall semen quality in a significant number of individuals. The treatment resulted in pregnancy in the partners of 14% of the patients.
Source : Evidence-Based Complementary and Alternative Medicine Volume 2011 (2011), Article ID 576962, 9 pages doi:10.1093/ecam/nep138
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