Treatment of Asthenozoospermia

Main article: Asthenozoospermia Overview

Treatment of Asthenozoospermia

Treatment of asthenozoospermia (also known as asthenospermia) can vary greatly according to the probable cause. The doctor may recommend you one or several treatments. Treatment options for men with low sperm motility include:

• Expectant management
• Lifestyle
• Supplements
• Environment
• Surgery
• Medication
• Assisted Reproductive Technology

Expectant Management

Expectant management means watchful waiting. This can be an option for men diagnosed with asthenospermia, especially if:

• the male patient is young and can make significant lifestyle changes.
• the female partner is also young and not diagnosed with any female infertility factors.

Experts suggest men diagnosed with low sperm motility can increase their sperm motility and chances of conception by trying at least every 1-2 days during the woman’s fertile window.
_{Source: Keihani S, et al. (2017); Hussein M, et al. (2008); Tur-Kaspa I, et al. (1994)}

It’s also important that popular lubricants (K-Y jelly, Durex) and natural lubricants (i.e., olive oil, saliva) are avoided, as they can impair sperm movement and function.

Lifestyle

Although there is limited evidence that lifestyle changes can treat asthenospermia, experts suggest the following lifestyle changes to increase sperm motility:

• Quit smoking
• Limit alcohol consumption (especially ALDH2*2 genotypes)
• Lose weight if obese
• Regular exercise to stay in good shape
• Consume a healthy and balanced diet

Limiting alcohol consumption is also important especially among East Asian men. This is due to changes in the ALDH2 gene (known as ALDH2*2) found in 40%-50% of East Asian men. A recent study revealed ALDH2*2 carriers have significantly lower progressive sperm motility (19% vs. 37%) and total sperm motility (20% vs. 41%) compared to non-carriers after consuming alcohol.

In a recent small trial, men with obesity (BMI ≥30 kg/m²) were randomized to 2 different diets to lose weight (with minimal exercise, restricted to resistance training <1.5 hours/week) over a 16 week period. At the end of the trial, the well-balanced low-energy diet of 800 kcal/day achieved the greatest weight loss and significantly improved both total and progressive motility for men with asthenospermia (n=3). Further studies are needed to understand these results.

It is widely agreed by experts nowadays that exercise should be done in moderation where possible. This is so as to minimise the impact of increased oxidant levels, caused by an increased consumption of oxygen from the skeletal muscles, on the natural balance of oxidants and antioxidants in the body. In this regard low-intensity exercise was shown minimise the percentage of abnormal sperm, compared to high-intensity exercise (17.4% vs. 25.1%), in a controlled rat study. The alternative to changing exercise routines may be as suggested to postpone one’s fertility until exercise plan and goals are complete, oxidant / antioxidant levels have returned to normal and pre-existing sperm expelled (2 -3 months).

A good healthy diet plan to follow suggested by experts is:

• To have at least 5 portions of vegetables and fruits daily (>734 g/day)
• High in fibre starchy food such as potatoes
• Some dairy or dairy alternatives
• Some protein such as beans, eggs, meat or fish

In a randomized group of healthy males, progressive (33.3% vs. 29.5%) and total motility (46.6% vs. 43.3%) parameters improved the most following a Mediterranean diet and increase in physical activity. This study used the PREvención con DIeta MEDiterránea (PREDIMED) and International Physical Activity Questionnaires (IPAQ), available online, to assess before and after diet and exercise levels and may be useful to self-evaluate your own diet and activity levels

Supplements

The following supplements can increase sperm motility:

• Alpha-lipoic acid
• L-arginine
• Carnitine
• Coenzyme Q10
• Zinc
• Selenium and Cysteine
• Magnesium
• Folate
• Vitamin E
• Vitamin D
• β‐carotene
• Resveratrol
• Synbiotics
• Antioxidants

Alpha-lipoic acid

Alpha-lipoic acid is an organic compound which serves as a broad antioxidant and reduces oxidative stress levels. In a placebo-controlled trial, featuring 80 males with idiopathic asthenospermia, 600mg of alpha-lipoic acid daily for 90 days significantly improved semen volume (2.9 vs. 1.8 ml), sperm count (15.2 vs. 48.0 10⁶/ml), total motility (54.3 vs. 11.4 %), progressive motility (42.4 vs. 11.7 %) and vitality (71.5 vs. 61.8 %). This result supports an earlier but smaller study finding improved sperm count, concentration and motility after alpha-lipoic acid supplementation in similar males.

L-arginine

L-arginine (also known as Arginine) is an important amino acid which participates in the process of spermatogenesis. It is involved in the inflammatory response and protects against oxidative damage, which may benefit males with mild inflammation or elevated levels of reactive oxygen species. Early studies identified a positive relationship between Arginase activity (linked to L-arginine) and sperm motility. A small trial of infertile men taking 1000mg of L-arginine daily for 4 months reported a doubling in motility, vitality and normal sperm, together with decreased oxidative stress and inflammation levels. Some good sources of arginine are meat, dairy products and nuts. Arginine supplementation is usually well tolerated however patients with genital/oral herpes, cancer and asthma should avoid.

Carnitine

The two most important isomers of carnitine are L-Carnitine and L-acetyl carnitine. Both can be formed inside the body. Carnitine is produced by modifying the amino acid Lysine, while acetyl carnitine is formed by enzymic addition of an acetyl group. According to the body needs, enzymes can convert carnitine to acetyl carnitine and vice versa. The main difference between these two isomers is that acetyl carnitine is more easily absorbed by the gut and can easily cross the blood-brain barrier.

Carnitines are found abundantly in spermatozoa, seminal plasma and even the epididymis to support spermatogenesis. Any deficiency is likely to affect sperm maturation and motility (via PI3K/AKT signalling pathway) which is improved with supplementation.

However, a recent animal study also suggests L-carnitine supplementation can potentially be toxic pending further studies. Therefore, supplementation should be reserved for diets deficient in L-carnitine (e.g. vegetarians). Good natural sources of carnitines are meat and dairy products.
_{Source: Ran L, et al. (2024)}

Coenzyme Q10

Coenzyme Q10 (CoQ10) is an endogenously synthesized fat‐soluble antioxidant plays a vital part in mitochondrial energy metabolism. Low CoQ10 seminal fluid levels effects sperm motility as well as other sperm parameters. Good natural sources of CoQ10 are fish, meat, nuts and plant-based oils such as soybean, corn, olive, and canola oils. Supplementation of CoQ10 (up to 300mg/day) is well tolerated although it has been reported to cause mild gastrointestinal symptoms in some people.

Zinc

Zinc a natural antioxidant, not stored in the body, is important to male fertility decreasing ROS levels, and increasing both sperm quantity and quality. Interestingly men with normal semen quality (sperm concentration, progressive motility and normal morphology) have higher seminal zinc levels (6.4 vs. 5.0 μmol/ejaculate) compared to men with one or more abnormal sperm parameters.

In subfertile males, pentoxifylline (a drug that improves blood flow) combined with zinc significantly improves sperm quality (concentration, progressive motility, morphology) than zinc alone after 3 months of supplementation. A simultaneous decrease in oxidative stress levels and inflammation was also observed.

However, a recent study also suggests that excess levels of zinc can be toxic to sperm requiring further studies. Therefore, supplementation should be reserved for diets deficient in zinc.
_{Source: Chen Y, et al. (2024)}

Selenium and Cysteine

Cysteine is an important component of glutathione synthesis. The higher the concentration of reactive oxygen species (ROS), the less glutathione is available in the body. N‐acetylcysteine (NAC), a precursor of the amino acid cysteine can be taken to help lower the concentration of ROS. A maximum dosage of 8000mg/day of NAC is believed to be safe and not linked to significant adverse events.

Similarly, selenium is directly involved in the mechanisms of cellular antioxidant defence. It increases glutathione peroxidase, which is an antioxidant enzyme. Consequently, any deficiency in selenium would make the human body more prone to oxidative injury. Selenium is also vital for normal spermatogenesis. However excess selenium levels is also toxic, causing damage to the testis and germ cells, leading to a significant decrease in sperm quantity and quality. Serum concentration of selenium between 110-165 μg/L is considered normal. Signs of excess selenium intake includes gastrointestinal side effects, hair loss, fatigue, joint pain and nail issues. Good natural sources of selenium are fish, meat and dairy products.

A few animal studies have reported positive effects of selenium on sperm parameters, however studies involving humans remain far and few. In 2009 a large RCTs concluded that 200µg Selenium and/or 600 mg N-Acetyl-Cysteine taken for 26 weeks was well tolerated among participants and improved all sperm parameters. Alahmar reported a similar result recently following selenium therapy in infertile males.

Parameters	Placebo	Selenium	NAC	Selenium + NAC
Volume (ml)	2.8	3.2	3.4	3.4
Sperm count (106)	52.9	60.8	58.3	71.2
Sperm concentration (106/ml)	23.5	27.6	26.8	32.1
Sperm motility (% motile)	22.9	26.1	24.8	29.2
Strict normal morphology (%)	7.2	9.2	9.2	9.3
Testosterone (nmol/l)	17.4	20.1	20.1	20.9

Magnesium

Magnesium is another micronutrient that is involved in the regulation of vitamin D and antioxidants. Green leafy vegetables, cereals, nuts and cereals are some good natural food sources of magnesium. Excessive intake of magnesium, via supplementation, can lead to abdominal cramping, nausea and diarrhoea.

Folate

Daily intake of folate (vitamin B9) commonly found in green leafy vegetables is low among the general population. However, it is an essential vitamin for the synthesis of protein, transfer RNA and DNA, which is crucial during spermatogenesis.

Vitamin E

Vitamin E, in the form of α‐tocopherol is believed to protect against oxidant‐induced membrane injury. Some good sources of Vitamin E are plant-based oils, nuts and seeds. Precaution should be taken not to exceed the daily recommended dose as excess vitamin E is reported to increase the risk of bleeding.

In males diagnosed with asthenospermia and teratospermia, Vitamin E (400 IU) and Selenium (200µg) combined, for 3 months, significantly improved sperm total motility (28.9% to 44.4%) and vitality (55.2% to 69.9%), with no change to the percentage of sperm with normal morphology. However, whether this result translates over to males diagnosed with asthenospermia only is the subject of future studies.

Vitamin D

A study in 2015 identified infertile males with low levels of vitamin D had significantly lower pregnancy rates following ovulation induction with timed intercourse. A more detailed study confirmed that vitamin D deficient (<20ng/ml) men have significantly reduced sperm count (23.5 vs. 67.2 millions/ml), motility (35.0 vs. 55.7 %) and sperm morphology (0.07 vs. 4.7 %) compared to men with normal vitamin D levels (>30ng/ml).

This correlates partially with the results of a placebo-controlled trial, where males diagnosed with asthenospermia and vitamin D3 (serum 25-OH-D3) levels < 30 ng/ml, were given 4000 IU of vitamin D3 to take daily for 3 months. At the end of the trial, both total and progressive sperm motility had improved significantly, along with calcium levels, while oxidative stress (MDA, TAC) decreased. Animal studies suggest vitamin D (along with calcium) improves the testosterone/estradiol ratio via a direct effect on the converting enzyme (aromatase: CYP19A1).

However, vitamin D deficient males are also recommended to check their magnesium levels, since vitamin D levels are strongly regulated by magnesium.

β‐carotene

β‐carotene, a provitamin A, is an important carotenoid that has the ability to directly scavenge ROS. Healthy young males with a higher carotenoid intake have consistently higher sperm motility. Good sources of β‐carotene are carrots, sweet potato, spinach, broccoli, kale, pumpkin, mango, apricot, and many yellow-orange fruits along with green leafy vegetables.

Note, Vitamin A supplementation if taken in excess is toxic and leads to hypervitaminosis A. On the other hand, excess intake of natural carotenoids is not linked with vitamin A toxicity, but can lead to yellow-tinged skin, also known as carotenaemia.

Resveratrol

Resveratrol is a polyphenol compound found in grapes, peanuts, berries, and wine. Resveratrol is described as having anti-inflammatory, cardioprotective, anticancer, antimicrobial, antiaging, and antioxidant effects. In a pilot study, twenty males diagnosed with idiopathic infertility (95% oligoasthenozoospermia meaning reduced sperm motility and low sperm count) took 150mg of resveratrol, every 12 hours, over a period of 6 months. At completion of the trial, significant improvements were seen in:

• Total sperm count (48 vs. 42 × 10⁶)
• Sperm concentration (26 vs. 23 × 10⁶/mL)
• Total motility (59% vs. 48%)
• Progressive motility (48% vs. 31%)

The authors noted that larger and more comprehensive studies are now required to confirm these findings and the mechanisms involved.

Synbiotics

In a triple-blinded randomized placebo-controlled trial, 500mg daily of probiotics combined with prebiotics (specifically FamiLact) for a total of 80 days significantly increased concentration (44.1 vs. 28.9 M/mL) and motility (50.8 vs. 38.4 %) in men strictly diagnosed with oligozoospermia, teratozoospermia and/or asthenozoospermia.

FamiLact contains a broad spectrum of Lactobacillus strains, including Lactobacillus rhamnosus / casei / bulgaricus / acidophilus, Bifidobacterium breve / longum, Streptococcus thermophilus (10⁹ CFU), with fructooligosaccharides as the prebiotic.

The researchers hypothesize that improvements in oxidative stress are most likely responsible for these results, given that the protamine content of sperm chromatin (CMA3 positivity) did not change, while DNA fragmentation levels decreased simultaneously (28.8% to 25.2%).

Antioxidants

There is some evidence that a combination of supplements, may be more effective at improving sperm motility compared to just a single supplement.
_{Source: Alahmar A T and Singh R, (2022); Scaruffi P, et al. (2021)}

Environment

Several studies have shown reduced sperm concentration and motility levels in summer, linked to both daily temperature and daylight hours. This is currently explained by maximum levels of estradiol, testosterone and LH, occurring in autumn which leads to higher sperm counts and thus higher number of total motile spermatozoa. However, whether this change remains true for males diagnosed with low sperm count or poor motility is unknown. In a more comprehensive study, humidity was also significantly linked to improved sperm quality.

Surgery

There are also cases were the cause of asthenospermia is linked to varicoceles. In such situations, the Doctor will normally recommend a couple treatment options before assisted reproductive technology.

Surgery (varicocelectomy) is proven to increase sperm count and total motility resulting in a significantly higher total motile sperm count and spontaneous pregnancy rates.
_{Source: Kalwaniya D S, et al. (2023); Majzoub A, et al. (2021); Boman J M, et al. (2008)}

However the combination of varicocelectomy and medication (ketotifen) or antioxidants (e.g. vitamin C) together improves sperm quality greater than either treatment on its own.
_{Source: Rezayat A A, et al. (2023); Fathi A, et al. (2021); Cyrus A, et al. (2015); Saharkhiz N, et al. (2013); Azadi L, et al. (2011)}

Medication

In cases of urogenital infection, antibiotics can be prescribed for treatment, simultaneously restoring fertility in most cases. Sperm parameters usually return to normal in males 6 months after pathogen eradication. Although, some pathogens are highly resistant to common antibiotics, possibly requiring specialist attention.

Assisted Reproductive Technology

Assited Reproductive Technology (ART) treatments involve obtaining sperm through normal ejaculation or surgical extraction, with donor sperm the last resort.

Semen quality is then improved via a variety of laboratory techniques:

• Swim up method
• Swim-up and Density Gradient Centrifugation
• Double tube method
• Magnetic-Activated Cell Sorting (MACS)
• Microfluidic sperm selection

Intrauterine insemination

Intrauterine insemination is a process by which collected sperm, concentrated in the lab, is then injected back into the woman’s uterus using a catheter to increase the chances of pregnancy per ovulation.

During this process, the greater the number of motile sperm inseminated, the more likely you are to achieve clinical pregnancy and live birth per IUI cycle. For reference, an extensive study showed males diagnosed with ‘mild male factors’ and a total progressive motile sperm count greater than 65.1 million (post-wash) achieved a clinical pregnancy rate of 14% and 10% live birth rate per IUI cycle. The use of post-wash sperm seems particularly important when the female partner is over the age of 28.

A large study using donor sperm in IUI cycles also reported that a timing interval (mismatch), between insemination to ovulation, greater than 19 hours, results in significantly reduced rate of clinical pregnancy and live births. Minimizing this difference should in effect maximize the probability of pregnancy per cycle.

Intracytoplasmic Sperm Injection

Intracytoplasmic Sperm Injection (ICSI) is an additional laboratory step carried out during the IVF treatment cycle. This involves the selection of a single sperm which is then injected into the egg to help increase the likelihood of fertilization.

As a result, ICSI is the treatment of choice in cases of asthenospermia since its success is not strictly linked to the results of basic sperm analysis or even the type of ultrastructural defect in the tail.
_{Source: Boursier A, et al. (2023)}

Nevertheless, studies show that ICSI treatment can be improved further with:

• Testicular sperm extraction
• Normal motility (≥25µm/s) sperm
• Short abstinence period
• Hyaluronic Acid

Chen et al. reported a downward trend in ICSI success rates according to the severity of asthenospermia, (progressive motile sperm, non-progressive motile sperm or immotile sperm). They concluded that males with complete asthenospermia (i.e. 100% immotile sperm) should consider testicular sperm extraction (TESE) to improve ICSI cycle outcomes.

A different study also reported that the selection of sperm with normal motility (≥25µm/s) and morphology is linked to reduced levels of DNA fragmentation (3.6% vs. 8.5%) which can be decreased even further using an experienced embryologist (2.6%) or computer-based software (1.3%). This explains why ICSI success rates is high for males diagnosed with asthenospermia.

Similarly, a short abstinence period (< 3 hour), can also improve sperm motility and DNA fragmentation significantly for males diagnosed with asthenospermia and oligospermia. This significantly increases the number of high quality embryos and may improve the ICSI success rate per cycle.
_{Source: Li Y, et al. (2023); Barbagallo F, et al. (2021); Hussein M, et al. (2008)}

Finally, in rare cases where the first ICSI cycle fails to result in an ongoing pregnancy the doctor may recommend hyaluronic acid sperm selection. This sperm selection technique more than triples the chance of a live birth (17% vs. 5%) in the next ICSI cycle for infertile couples.

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