Treatment of Low Sperm Count

Main article: Low Sperm Count Overview

Treatment of Low Sperm Count

Once a diagnosis has been made, your Doctor will recommend one (or a combination) of the following treatment options for low sperm count:

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

Expectant Management

Expectant management means watchful waiting. This can be an option for males diagnosed with mild oligozoospermia, especially if:

• the male patient is young and has been trying to conceive less than 12 months.
• the female partner is also young and not diagnosed with any female infertility factors.

In fact, studies show a significant number of men diagnosed with low sperm count, after only 12 months of unprotected intercourse, manage to conceive naturally in the next 12 months, by trying at least every 1-2 days during the woman’s fertile window.
_{Source: Keihani S, et al. (2017); Barak S and Baker HWG, (2016); Tur-Kaspa I, et al. (1994)}

Moreover, a shorter abstinence period of 1 to 2 days is actually helpful to some men with low sperm count. Studies show that ejaculatory abstinence beyond 24 hours significantly decreases sperm count in males diagnosed with oligospermia. Although this is only likely to be true for men with elevated oxidative stress levels.

Experts also recommend men with low sperm count to avoid lubricants, including saliva, where possible during intercourse as this can impair sperm movement and function.

Lifestyle

Although there is limited evidence that lifestyle changes can directly improve male fertility, according to derivable evidence experts suggest that the following lifestyle changes can maximise the chances of conceiving:

• Quitting smoking
• Limiting alcohol consumption
• Lose excess weight
• Regular exercise to stay in good shape
• Adequate and timely sleep
• Consuming a healthy and balanced diet

Quitting smoking is particularly effective for heavy smokers (≥ 20 cigarettes/day) with significant increases in semen volume (+17%), sperm concentration (+23%) and sperm count (+45%) reported after just 3 months.

Losing weight may also help improve sperm concentration and total sperm count in some cases. Studies show overweight men (BMI>30) who manage to lose weight (9+kg) by consuming an energy restricted diet for 3 months will slowly improve their testosterone levels (10+%) and possibly even sperm count in the following 9 months post-diet. Unfortunately both studies did not feature men with low sperm count so these results may or may not be relevant. Animal studies suggest lipid deposition in the testes is a contributing factor to obesity-related male hypogonadism.
_{Source: Yu C, et al. (2019); Moran L J, et al. (2016); Morgan D H, et al. (2014); Håkonsen L B, et al. (2011)}

Similarly, exercise can also improve testosterone levels and thus sperm quality. However, exercise should only be done in moderation where possible to minimise the effect of higher oxidant levels (caused by increased consumption of oxygen from the skeletal muscles) on the natural balance of oxidants and antioxidants in the body. In a controlled rat study, low-intensity exercise significantly decreased the percentage of abnormal sperm, compared to high-intensity exercise (17.4 vs 25.1%). This finding is supported by human trials, which found 30 mins of endurance running at 70% intensity per week significantly increased testosterone levels more than other regular forms of exercise (endurance interval running, resistance training, explosive training, speed-endurance 50m, speed-endurance 150m). An earlier study also revealed this type of exercise (specifically jogging and walking) is more effective than dieting on testosterone levels in obese men.

Alternatively, experts suggest males postpone trying to conceive until current exercise plan and weight goals are complete, oxidant / antioxidant levels have returned to normal and pre-existing sperm expelled (2-3 months). This was demonstrated in a recent trial. Obese males (BMI 32 to 43 kg/m²) who lost at least 16.8kg after an 8-week low calorie diet and maintained the weight loss for 12 months (via moderate physical activity), significantly increased sperm count and concentration. This also led to a small reduction in the number of males who were still diagnosed with oligospermia at the end of the trial.

In cases of obesity induced hypogonadism (BMI > 35), metabolic surgery (Roux-en-Y Gastric bypass) improved male hormone levels across the board, with significant increases seen in luteinizing hormone (3.4 vs 2.4 mUI/mL), sex hormone-binding globulin (41.1 vs 27.7 nmol/L), free testosterone (7.4 vs 5.2 ng/dL) and total testosterone (417.3 vs 263.8 ng/dL), along with decreased estradiol levels (38.2 to 28.3 pg/mL), 12 months post-surgery in 15 males. This improvement in hormone levels was accompanied by increased semen volume (2.0 to 3.0 mL, 12 months post-surgery), sperm count, progressive motility (43.1 to 59.2%), normal sperm percentages (4.9 to 7.6%, 6 months post-surgery), DNA integrity, mitochondrial activity and lipid peroxidation (12 months post-surgery).

Similarly, in an IVF study featuring obese males with unexplained infertility, sperm quality significantly improved following sleeve gastrectomy, leading to a significant increase in the mean number of fertilised embryos, top-quality embryos, implantation rate, pregnancy rate and live birth rates.

However, improvement in sperm quality is not always guaranteed due to a lack of nutrients, the release of endocrine disrupting chemicals or other toxic compounds from adipose tissue.

Likewise, sleep bedtime and duration is also a complex balance. Every individual falls into one of 4 sleep chronotypes, with any deviation from an individuals natural circadian rhythm directly impacting sperm counts. A recent study calculated the effect of such a change in sleep midpoint alone on non-work days (predominantly weekends) in 3 different groups: Group 1 = 0.64 ±0.49 hr, Group 2 = 0.88 ±0.54 hr, Group 3 = 1.32 ±0.67 hr, finding an independent decrease in sperm count of 9.3%, 12.8% and 19.2% respectively. Likewise sleep duration independently affects sperm count however changing sleep duration towards 7.0–7.5 hr/day reverses this effect.

Unsurprisingly 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

A randomized controlled trial showed that both the Mediterranean diet and low-fat diet, improves semen parameters in healthy males. Interestingly a higher sperm concentration and total count was seen in the Mediterranean diet group, however whether this result would repeat in males featuring low sperm counts is unknown.

In another randomized group of healthy males, overall sperm quality also improved, 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 count:

• Zinc
• L-carnitine
• Coenzyme Q10
• Folic acid
• Panax ginseng
• Mucuna pruriens
• Nigella sativa
• Horse chestnut
• Vitamin D
• Vitamin B12
• Resveratrol
• Selenium
• Synbiotics
• Antioxidants
• Others

Zinc

Several studies have shown the importance of zinc in male fertility, particularly as zinc is not stored in the body. Men with seminal Zinc deficiency have significantly lower semen volume, total sperm count, sperm concentration, progressive motility and serum testosterone levels.

Of note, pentoxifylline (a drug that improves blood flow) and zinc combined significantly improves sperm quality (concentration, progressive motility, morphology) more than zinc alone in subfertile males after 3 months.

L-carnitine

L-carnitine is a compound with potent antioxidant properties that specifically inhibits lipid peroxidation. In 2015, a systemic review concluded that L-carnitine supplementation simultaneously improves semen parameters and the chances of spontaneous pregnancy for men with no adverse reactions.

A mechanistic study revealed that L-carnitine (via the PI3K/AKT signalling pathway) decreases sperm cell death leading to increased sperm count and significantly greater motility, confirming an earlier study.

However, a recent animal study suggests L-carnitine supplementation could potentially be toxic pending further studies. Therefore, supplementation should be reserved for diets deficient in L-carnitine (e.g. vegetarians).
_{Source: Ran L, et al. (2024)}

Coenzyme Q10

Coenzyme Q10 (CoQ10) has a bioenergetic and antioxidant role in the body. It is also found in seminal fluid where its concentration is directly associated with sperm count and motility. Supplementation is recommended in males where CoQ10 delivered through ones diet is low. High levels of CoQ10 is found naturally in pork, beef, chicken, liver, mackerel, pistachios, peanuts and sesame seeds.

Folic Acid

Daily intake of vitamin B9 (folate) 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 the main part of spermatogenesis. To test the importance of folic acid a double-blinded, randomized, placebo-controlled trial was carried out in both fertile and subfertile men who took 5mg of folic acid daily for a period of 26 months. At the end of the trial period folic acid supplementation significantly increased sperm concentration and total sperm count in subfertile men, whilst having no significant effect on fertile men.

Panax ginseng

The pharmacologically active component of ginseng, ginsenosides, are triterpenoid saponins that structurally resemble the steroid hormones (androgen, estrogen, progesterone). Various studies have identified Rb1, Re, Rg1, Rg3 and Rh1 type ginsenosides to be steroid receptor agonists altering spermatogenesis and improving sperm count, concentration and motility via various pathways. Panax (asian) ginseng is known to increase total and free testosterone levels, in oligoastenospermic patients and age matched healthy controls, leading to a subsequent increase in sperm concentration and motility for both groups.

Mucuna Pruriens

Mucuna pruriens (or itching bean) is a traditional medicinal plant. The active substance L-DOPA has strong antioxidant effects, however it is less effective than mucuna pruriens extract and is reported to have adverse effects. In the only human study to date, 5g/day of mucuna pruriens significantly increased sperm count and reduced cortisol levels in men with stress induced oligozoospermia. Animal studies support this finding showing mucuna pruriens treatment restores hormone levels entirely (testosterone, FSH, LH) and protects the testis, epididymis and germ cells from damage.

Nigella sativa

Also known as ‘black seeds’ is a plant belonging to the Ranunculaceae family. widely known as a medicinal plant among the middle east with anti-inflammatory, antimicrobial and antioxidative properties. Various animal and human studies have consistently shown improvement in overall sperm quality with the only clinical trial (randomized double-blind placebo-controlled trial) thus far confirming a significant increase in sperm count, motility, volume and pH levels following 5mL per day of Nigella sativa oil for 2 months in infertile men.

Horse chestnut

In varicocele-associated infertility escin (horse chestnut) was originally proposed following successful use in treating a variety of chronic venous malfunctions. Escin is reported to have anti-inflammatory, anti-edematous and venotonic properties. In males with mild, moderate and severe varicocele, 300mg of escin daily for 2 months improved sperm density and motility in the majority of patients. Interestingly escin showed maximum efficacy in patients with mild and moderate varicocele, although surgery was shown to be most effective overall.

Vitamin D

Vitamin D is another antioxidant of interest in humans due to commonly low levels of this vitamin among the general population. A previous study identified infertile males with low levels of vitamin D had significantly lower pregnancy rates following ovulation induction with timed intercourse. This was supported by another study showing vitamin D levels <20 ng/mL significantly increased the risk of pregnancy loss (adjusted odds ratio 9.0).

In a more recent study, males classified as vitamin D deficient (<20ng/ml) had 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 those with sufficient levels (>30ng/ml). This study found no correlation between vitamin D levels and oxidative stress markers suggesting vitamin D effect on spermatogenesis occurs via an alternate pathway, and not as an antioxidant. Animal studies suggest vitamin D (along with calcium) improves the testosterone/estradiol ratio via lipid metabolism (CYP11A1, CYP19A1).

A recent interventional study revealed vitamin D supplementation (2500 IU/day) over 6 months increased sperm concentration (15.3 to 19.7 million/ml), and thus sperm count, in 34 infertile and vitamin D deficient males. This moderate change is enough to increase the chances of live birth by 50% according to Jensen et al. during treatment (over 5 months).

Vitamin B12

Vitamin B12 is an essential water-soluble vitamin that plays a critical role in homocysteine’s remethylation cycle. Some infertile men have significantly lower levels of vitamin B12 which may be exacerbated by diet (vegan). Various small studies report that vitamin B12 supplementation can sometimes improve sperm count, motility and DNA fragmentation. Recent human and animal studies show that vitamin B12 also protects the testicles from damage which improves testosterone levels.
_{Source: Panal M R, et al. (2024); Karabulut D, et al. (2021); Banihani S A, (2017); Dhillon V S, et al. (2007); Iwasaki A, et al. (2003); Isoyama R, et al. (1984)}

Resveratrol

A polyphenol compound found in grapes, peanuts, berries, and wine described as having anti-inflammatory, cardioprotective, anticancer, antimicrobial, antiaging, and antioxidant effects was evaluated 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 (48.2 × 10⁶ vs 41.5 × 10⁶)
• Sperm concentration (25.7 × 10⁶/mL vs 22.6 × 10⁶/mL)
• Total motility (59.0% vs 48.3%)
• Progressive motility (48.3% vs 31.0%)

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

Selenium

Selenium is vital for normal spermatogenesis and antioxidant levels. Consequently, any deficiency (or increase) in selenium is likely to have an impact on all sperm parameters to some degree.

For example, infertile males diagnosed with oligoasthenoteratospermia, who took 200μg/day of selenium for 6 months reported significantly increased sperm count, sperm motility and normal morphology, along with significantly decreased sperm DNA fragmentation and oxidative stress levels.

On the other hand excess selenium levels is in fact toxic to the body, 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.

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 ±24.97 vs 28.85 ±17.1 M/mL) and motility (50.81 ±34.94 vs 38.4 ±25.08 %), 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 hypothesise 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.

Antioxidants

Adequate antioxidant levels are essential for spermatogenesis especially as men get older (e.g. vitamin C). In cases of poor diet or genetic blockades, a combination of antioxidants may be more effective than just one for spermatogenesis. A recent placebo-controlled trial Patki et al. reported taking a combination of antioxidants daily for 3 months significantly increased sperm count in men with oligospermia. In fact, the more severe the case of oligospermia, the greater the effect antioxidant supplementation had on sperm count. Nevertheless, further trials are required to support these preliminary results.

Others

A variety of other supplements have been shown to increase sperm count in animal studies only to date.

Black soybean tempah	Gofur A, et al. (2020)
Ellagic acid	ALTamimi J Z, et al. (2021)
Esculetin	Türk E, et al. (2020)
Glutathione	Abdullah F, et al. (2021)
Grape seed extract	Abdulwahab D K, et al. (2020)
Oyster peptide	Jin Q G, et al (2021) Jin Q, et al. (2021)
Purple sweet potato	Gofur A, et al. (2020)

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 directly leads to higher sperm counts. However whether this change remains true for males diagnosed with low sperm count is unknown. In a more comprehensive study, increased humidity was also significantly linked to improved sperm quality.

Surgery

Blockages in the ejaculatory ducts and varicoceles can be surgically corrected. Studies show varicocelectomy is beneficial even in males with normal semen parameters (but high DNA fragmentation) or severe oligozoospermia (Total Motile Sperm Count < 5 million), with statistically significant improvements in sperm count, total motility, DNA fragmentation and sperm capacitation (the ability to penetrate and fertilise an egg).
_{Source: Tan L V, et al. (2023); Fathi A, et al. (2021); Majzoub A, et al. (2021); Gaffney C, et al. (2020)}

A graphical calculating device (nomogram) developed to predict sperm improvements and chances of spontaneous pregnancy after varicocelectomy suggest that men with higher testosterone levels but low sperm concentration, larger diameter veins and poor testicular tissue health are most likely to see an improvement in sperm parameters and fecundability post-surgery.

A recent placebo controlled trial reported that 12 weeks of probiotic supplementation after varicocele surgery significantly increased sperm concentration and count more than the placebo in men with normospermia. However, whether or not this effect is the same in males with low sperm count after varicocelectomy is yet to be confirmed.
_{Source: Asadi M, et al. (2023)}

In other cases (i.e. unsuccessful vasectomy reversal) where insufficient sperm is ejaculated, sperm can also be retrieved directly from the testicles or the epididymis through a variety of sperm retrieval techniques (TESA, TESE, micro-TESE).

Medication

The following medication is used to restore or increase sperm count:

• Antibiotics
• Anti-inflammatory drugs
• Hormone therapy
• Sexual dysfunction specific

Antiobiotics

Antibiotics is normally prescribed for treating an infection however, in some cases, fertility is not always restored. In the majority of cases sperm parameters return to normal 6 months after pathogen eradication. Although, some pathogens are highly resistant to common antibiotics, possibly requiring specialist attention.

Anti-inflammatory drugs

Anti-inflammatory drugs can increase sperm count in some cases. Specifically, men who experience a decline in total motile sperm count (TMSC) 3 months after vasectomy reversal. Six weeks of low-dose prednisone treatment reportedly stops inflammatory scarring and significantly increases TMSC (+6 million).
_{Source: White J, et al. (2024); Machen G L, et al. (2020)}

Hormone therapy

Men diagnosed with low sperm count and hormone imbalance can be treated with one of the following hormone therapy options:

• Follicle-Stimulating Hormone
• Human Chorionic Gonadotropin
• Aromatase Inhibitors
• Clomiphene Citrate

Follicle-Stimulating Hormone

Follicle-Stimulating Hormone (FSH) treatment is successful in 25-35% males diagnosed with oligozoospermia. Specifically males with normal FSH, inhibin B or progesterone levels, and testicular volume. Researchers report this is due to variations in the FSH or CYP17A1 gene.

In one small study, daily administration of FSH (75 IU) over 3 months, to a group of 24 males, of which only 8 responded positively, significantly improved the group mean sperm parameters: sperm concentration (+100%), total sperm count (+50%); progressive motility (+70%); sperm morphology (+55%); sperm vitality (+100%) and DNA fragmentation (-35%).

Human Chorionic Gonadotropin

Human Chorionic Gonadotropin (hCG) treatment is successful in over 80% of males with low sperm count and concentration. Especially males with similar LH and FSH levels, but low or borderline total testosterone levels and free testosterone > 10 pg/mL. Andrabi et al. reported that a weekly dose of hCG (6500 IU) more than doubles mean sperm concentration and count after just 3 months among men with severe oligozoospermia.

Aromatase Inhibitors

Aromatase inhibitors such as anastrozole are suited to males with low sperm count and abnormal testosterone/estrogen ratio (T/E <15) or testosterone/LH ratio (T/LH >100). Aromatase inhibitors block the conversion of testosterone into estradiol, and androstenedione to estrone, which increases testosterone levels and improves sperm parameters. Several studies report that 3 months of anastrozole therapy is sufficient to treat oligozoospermia irrespective of BMI (<24 or ≥24).

Clomiphene Citrate

Clomiphene citrate treatment is best suited to males with low FSH and LH levels, which impairs testosterone levels (< 300 ng/dL) and total sperm count. Clomiphene citrate blocks the bodies natural reading of estradiol levels which causes the release of more FSH and LH, and increases the production of testosterone in the testis (via leydig cells). Unfortunately, studies show that clomiphene citrate treatment needs to continue for at least 9 months before significant changes in sperm count are seen. Nevertheless, long-term use of clomiphene citrate is potentially a safe and effective option for males diagnosed with functional hypogonadotropic hypogonadism (e.g. obesity).

Interestingly, clomiphene citrate treatment could potentially be improved with diet (e.g. cashew nuts). Akomolafe et al. reported that clomiphene citrate treatment plus cashew nuts significantly improved all semen parameters, compared to either option alone, in a controlled animal study. Although cashew nuts are high in zinc, they also contain many phenolic compounds which could have contributed to this result requiring further studies.

Sexual dysfunction specific

Counselling and medications may help to improve fertility in conditions such as premature ejaculation and erectile dysfunction.

Assisted Reproductive Technology

Assisted 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

However in some specific cases, your Doctor may recommend obtaining sperm via surgery, otherwise known as testicular sperm extraction (TESE). TESE is a surgical procedure whereby a small incision is made in the testicles to extract sperm and or tissue containing sperm. This is sometimes beneficial in severe cases of oligospermia, particularly patients with testicular cancer. However surgery always carries additional risks and the potential for complications requiring careful consideration.

In a recent study, microscope assisted TESE (micro-TESE) was compared to testicular sperm aspiration (TESA), in men with severe oligozoospermia. The author reported no difference in the rates of successful sperm recovery between TESA at 95% (18/19 males) and micro-TESE at 92% (60/65 males).

Intrauterine insemination

Intrauterine insemination is a process by which collected sperm, concentrated in a lab, is then injected 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.

In cases of low total motile sperm count (TMSC) < 5 million, an alternate study reported giving a second ejaculate sample within 1 hour of the first sample doubled the inseminating motile count to 9.01 million resulting in a clinical pregnancy rate of 15.6%. This compared favourably to the control group (normozoospermic males), which achieved a clinical pregnancy rate of 15.4%.

Similarly, a timing interval (or mismatch) between insemination to ovulation greater than 19 hours, results in significantly decreased rates of clinical pregnancy and live birth, as reported in a large study using donor sperm. Minimizing this difference should in theory maximize the probability of pregnancy per IUI cycle.

Intracytoplasmic Sperm Injection

Intracytoplasmic Sperm Injection (ICSI) is an additional laboratory step carried out during an IVF treatment cycle. This involves the selection of a single sperm, from males predominantly with severe oligozoospermia, which is directly injected into the egg to help increase the likelihood of fertilisation.

ICSI is successful even in genetic cases of severe oligozoospermia (i.e. AZFc microdeletions) although success rates are significantly impaired when sperm concentration is <1 million/mL.
_{Source: Zhang H, et al. (2024)}

In cases where ICSI fails to fertilise a majority of eggs, experts suggest switching to testicular sperm to significantly increase the number of embryos developing through to day 3.

In males affected by anti-sperm antibodies (ASA), a study comparing positive and negative ASA males, failed to find any significant difference in the rate of fertilisation, pregnancy or number of grade A embryo’s following standard ICSI.

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