Treatment of Teratozoospermia

Treatment of Teratozoospermia

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

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

Expectant Management

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

• the male patient is young, has normal sperm count and motility, been trying to conceive less than 24 months, and diagnosed as idiopathic (unknown) infertility.
• the female partner is also young and not diagnosed with any female infertility factors.

In cases of severe teratozoospermia (or 0% normal sperm morphology), a comparative study showed 25% of men diagnosed with severe teratozoospermia successfully fathered their first child naturally over a period of 2.5 years. This compared to 52% of control men with normal sperm quality over the same period. For reference, males with severe teratozoospermia in this study also had, on average, abnormal sperm count (18.9 million) and total motility (29.1%) results.
_{Source: Kovac J R, et al. (2017)}

Lifestyle Modification

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
• Reducing weight if obese
• Regular exercise to stay in good shape
• Consuming a healthy and balanced diet
• Avoiding lubricants during intercourse

Obesity is consistently linked to poor sperm quality including lower percentages of normal sperm morphology. In the only study of its kind, 43 obese males (BMI > 33kg/m²) participated in a 14 week weight loss program. At the end of the program, obese males who managed to lose at least 12% of body weight significantly increased testosterone and SHBG levels leading to improved sperm parameters. In fact, males who managed to lose the most weight (>17%) significantly increased normal sperm morphology (+4%) beyond the WHO lower limit.
_{Source: Hakonsen L B, et al. (2011)}

However, exercise where possible should be done in moderation 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 routine may be as suggested to postpone ones fertility until exercise plan and goals are complete, oxidant / antioxidant levels have returned to normal and pre-existing sperm expelled (2-3 months).
_{Source: Hosseini M, et al. (2021)}

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, sperm cells with normal morphology was significantly higher (7.6% vs. 5.8%) in men who followed a Mediterranean diet and increased their physical activity (i.e. walking 20mins/day). This study used the PREvención con DIeta MEDiterránea (PREDIMED) and International Physical Activity long form 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.
_{Source: Montano L, et al. (2021); Martínez-González M A, et al. (2012); Hagströmer M, et al. (2006)}

Lastly it is important that popular lubricants (i.e. K-Y jelly, Durex) and natural lubricants (i.e. olive oil, saliva) are avoided, as they can impair the movement and function of otherwise normal sperm. Instead only genuinely sperm-safe lubricants should be used only as required (i.e. egg-white).
_{Source: Markram J, et al. (2022); Soriano M J, et al. (2021)}

Medication

In cases of urogenital infection, antibiotics can be prescribed for treatment, simultaneously restoring fertility in most cases. Generally speaking, sperm parameters return to normal 6 months after pathogen eradication. However, in cases of chlamydia trachomatis, a significant improvement in sperm morphology was reported just 2 weeks after completing treatment.
_{Source: Makarounis K, et al. (2022); Yasynetskyi M, et al. (2021)}

Surgery

It is common to find poor sperm quality including morphology in men with varicoceles. Varicoceles can be treated with surgery (i.e. varicocelectomy) although only men with teratozoospermia and clinically palpable varicoceles are likely to see an improvement in sperm morphology post-surgery. Varicocelectomy also outperforms antioxidant supplementation after 6 and 12 months.
_{Source: Dursun M, et al. (2024); Yaris M and Kilinc R, (2022); Fathi A, et al. (2021); Morini D, et al. (2021); Birowo P, et al. (2020); Ilktac A, et al. (2020)}

	Antioxidants		Varicocelectomy
	(Before)	(After)	(Before)	(After)
Sperm concentration (million)	25	26	24	28
Progressive motility (%)	36	37.5	36.5	40
Normal morphology (%)	0.9	1.5	1	3.5
DNA fragmentation (%)	33	29	32	25
Patients with normal morphology (%)	0	25	0	49
Pregnancy at 6 months (%)		0		8.3
Pregnancy at 12 months (%)		16.7		30.5

Interestingly, varicocelectomy followed by vitamin C (i.e. antioxidant) supplementation for 3 months significantly increases sperm morphology more than the placebo controlled group post-surgery.
_{Source: Cyrus A, et al. (2015)}

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

Supplements

A Cochrane review concluded that there is low-level evidence that supplementation with antioxidants may be beneficial for subfertile males in improving live birth rates and clinical pregnancy rates. Although only 7 small randomised controlled trials were reviewed.

Fortunately, in cases of teratozoospermia, there are studies which show some supplements have a positive impact on sperm morphology.

These supplements are:

• Lycopene
• Coenzyme Q10
• Cysteine and Selenium
• Zinc and Folate
• Vitamin C
• Vitamin D
• Multi-vitamin

Lycopene

Lycopene is a carotenoid, with antioxidant properties, that is responsible for the red and pink colours of many fruits and vegetables. In an earlier cross-sectional study, involving 189 healthy university-aged males, higher consumption of lycopene (>8610μg/day), equivalent to 3 tomatoes, was linked to better sperm morphology. To test this further, a randomized placebo-controlled trial, tested lactolycopene. Lactolycopene is lycopene with whey protein combination designed to enhance lycopene absorption. Healthy males taking 14mg/day of lactolycopene for 12 weeks, showed significantly improved sperm morphology (13.5% vs. 7.5%). However, both these studies were limited to healthy males, meaning lycopene supplementation in men with teratozoospermia may produce different results.
_{Source: Williams E A, et al. (2019); Zareba P, et al. (2013)}

Coenzyme Q10

CoQ10 an endogenously synthesized fat‐soluble antioxidant which is effective against high-fat diets. Low CoQ10 seminal fluid levels significantly affects sperm concentration, motility and morphology.
_{Source: Allam E A, et al. (2022)}

Two recent studies indicate a dose-dependent relationship between CoQ10 supplementation and the improvement in sperm quality. Males diagnosed with Oligo-astheno-teratozoospermia responded better to 400mg/day of CoQ10, with significantly better concentration, progressive motility and total motility. Sperm morphology also trended higher in this direct comparison of 200mg/day vs. 400mg/day. However other studies clearly show that longer CoQ10 treatment (6-12 months) significantly improves sperm morphology over time.
_{Source: Bahar T G, et al. (2023); Alahmar A T, et al. (2021); Alahmar A T, (2019); Safarinejad M R, et al. (2012); Safarinejad M R, et al. (2011)}

Good natural sources of CoQ10 are fish, meat, nuts and plant-based oils such as soybean, corn, olive, and canola oils. Supplementation of CoQ10 is well tolerated although it has been reported to cause mild gastrointestinal symptoms in some people.

Cysteine and Selenium

Cysteine and Selenium each play a unique but also similar role in managing oxidative stress. 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. A natural precursor of cysteine is N‐acetylcysteine (NAC), which helps lower the concentration of ROS in the human body.
_{Source: Atkuri K R, et al. (2007)}

Similarly, selenium is also involved in the mechanisms of cellular antioxidant defence. It increases glutathione peroxidase, which is an antioxidant enzyme. Consequently, a deficiency in selenium makes the human body more prone to oxidative injury. Detailed studies show that selenium is 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. For reference, 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.
_{Source: Xu Z J, et al. (2023); Zhang Y, et al. (2023); Steinbrenner H, et al. (2022); MacFarquhar J K, et al. (2010); Boitani C and Puglisi R, (2008); Burk R F, (2002)}

In a large placebo-controlled trial, N-acetylcysteine (600mg) plus selenium (200µg) supplementation over 26 weeks improved sperm count, concentration, motility and normal morphology, along with testosterone levels (17.4 to 20.9 nmol/l) in subfertile males.
_{Source: Safarinejad M R and Safarinejad S, (2009)}

Zinc and Folate

Zinc and folate are both essential nutrients for the human body. Folate (vitamin B9), commonly found in green leafy vegetables, is low among the general population. Although it is an essential vitamin for the synthesis of protein, transfer RNA and DNA, which is a main part of spermatogenesis.
_{Source: Joshi R, et al. (2001)}

However, various studies show that a deficiency in zinc also decreases the absorption and metabolism of folate, as does polymorphisms in the MTHFR gene.
_{Source: Ebisch I M, et al. (2006)}

Zinc is commonly found high in red meats (beef, lamb), oysters, crab and pumpkin seeds. Zinc is a natural antioxidant which is not stored in the body. However, zinc is equally important to male fertility, decreasing ROS levels, and increasing both sperm quantity and quality.
_{Source: Colgar A H, et al. (2009)}

Osadchuk et al. reported that men with normal semen quality (sperm concentration, progressive motility and normal morphology) had higher seminal Zinc levels (6.4 vs. 5.0 μmol/ejaculate). Meanwhile a recent animal study revealed zinc deficiency significantly increases abnormal sperm morphology and oxidative stress.
_{Source: Sun B, et al. (2023); Osadchuk L, et al. (2021)}

However, combined zinc and folate supplementation is only likely to benefit subfertile males with known zinc and folate deficiencies or genetic causes. While excess zinc and folate consumption is likely to cause more adverse events.
_{Source: Schisterman E F, et al. (2020); Ebisch I M, et al. (2006)}

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.
_{Source: Dadgar Z, et al. (2022)}

Vitamin C

Studies report vitamin C (ascorbic acid) reduces sperm DNA damage directly by removing free radicals and lowering the formation of lipid hydroperoxides. In fact, concentration of vitamin C is up to 10 times higher in seminal plasma than blood plasma. This highlights the significant role vitamin C plays in protecting sperm from oxidative stress. Lower levels of ascorbic acid in seminal plasma has been linked to abnormal morphology and a higher risk of sperm DNA damage.
_{Source: Smits R M, et al. (2019); Colagar A H and Marzony E T, (2009); Padayatty S J, et al. (2003)}

Supplementation wise, fruits and vegetables remain some of the best sources of Vitamin C. This includes guavas, bell peppers (capsicum), kiwifruit, strawberries, oranges, papaya, broccoli, tomato, snow peas and brussel sprouts.

Vitamin D

Males classified as vitamin D deficient (<20ng/ml) were found to 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 males with sufficient levels (>30ng/ml). This result is similar to that reported in animal studies which also suggest vitamin D (along with calcium) improves the testosterone/estradiol ratio via a direct effect on the converting enzyme (aromatase: CYP19A1).
_{Source: Pouriayevali F, et al. (2022); D’Andrea S, et al. (2021); Hajianfar H, et al. (2021); Shahid M, et al. (2021); Azizi E, et al. (2018); Jensen M B, et al. (2016)}

No vitamin D supplementation trials have been carried out in men specifically diagnosed with teratozoospermia. However, males significantly deficient in vitamin D should increase their vitamin D levels, for a full spermatogenesis cycle (3 months). This will improve your overall health and confirm whether or not vitamin D deficiency was a contributing factor in your circumstance.

Multi-vitamin

The use of fertility specific multi-vitamins in subfertile males repeatedly shows benefits above and beyond trials of individual ingredients. This suggests multi-vitamin use has a synergistic effect on spermatogenesis and/or a much broader treatment range, requiring further studies.

In one placebo-controlled study, daily intake of an antioxidant based multi-vitamin, over 4 months, significantly increased sperm concentration, progressive motility and normal morphology. During this period, the proportion of males originally diagnosed with 3 or more abnormal sperm parameters, also decreased from 40.5% to just 7.1%. Interestingly, 10/42 (24%) couples from the multi-vitamin group got pregnant, over the 6 month study period, compared to just 2/41 (5%) of couples from the placebo group.
_{Source: Kopets R, et al. (2020)}

A similar trend was noted in another placebo-controlled study, using a different antioxidant based multi-vitamin formulation, with improvements in both sperm parameters and pregnancy rates, among the multi-vitamin group.
_{Source: Busetto G M, et al. (2018)}

Assisted Reproductive Technology (ART)

ART treatments involve obtaining sperm through normal ejaculation or surgical extraction, with donor sperm a last resort in severe cases.

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

Unfortunately these techniques only increase the concentration of morphologically normal and motile sperm, with low levels of DNA damage, in the semen sample rather than repair damage spermatozoa. This is why your Doctor may recommend other treatment options first.

Intrauterine Insemination

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

Studies show that teratozoospermia has no significant effect on the live birth rate per IUI cycle (even though there is a minor effect on clinical pregnancy rates per IUI cycle). This remains true irrespective of sperm morphology percentage (i.e. 1%, 2%, 3%, or 4%).
_{Source: Pavlovic Z J, et al. (2024); Sayegh L, et al. (2024); Stanhiser J, et al. (2020)}

In fact, in subfertile males with either abnormal sperm sperm count, progressive motility or normal morphology, only total progressive motile sperm count (TPMSC) significantly influences clinical pregnancy rates and live birth rates per IUI cycle. For this reason, Shabtaie and co. proposed that subfertile males diagnosed with teratozoospermia, but normal sperm concentration and motility, and no female factors consider IUI before IVF.
_{Source: Lin H, et al. (2021); Shabtaie S A, et al. (2016)}

One explanation for significantly lower success rates of IUI, compared to IVF, is possibly poor timing of insemination and ovulation. Specifically, a timing mismatch greater than 19 hours, between insemination and ovulation, results in significantly reduced rates of clinical pregnancy and live births.
_{Source: Mu X, et al. (2021)}

After the fourth IUI cycle, unsuccessful couples should consult their Doctor and consider IVF.
_{Source: Starosta A, et al. (2020)}

In Vitro Fertilization

In Vitro Fertilization (IVF) plus Intracytoplasmic Sperm Injection (ICSI) is often recommended to subfertile couples diagnosed with male factor infertility. This involves the selection of a single sperm cell which is then injected into the egg to help increase the likelihood of fertilization.

However in cases of isolated teratozoospermia, several studies show IVF with ICSI fails to increase the clinical pregnancy rate, or live birth rate per cycle compared to standard IVF. This may be due to the chance selection of dying or DNA damaged sperm as studies utilising Magnetic-Activated Cell Sorting (MACS) show improved clinical outcomes particularly among older women.
_{Source: Norozi-Hafshejani M, et al. (2022); Pacheco A, et al. (2020); Woolnough B, et al. (2020); Fan W, et al. (2012); Keegan B R, et al. (2007)}

Nevertheless, there is ample evidence that ICSI presents additional risks and should only be used in limited circumstances (e.g. globozoospermia, acephalic spermatozoa syndrome or tail defects) which may also require assisted oocyte activation to achieve fertilization. These defects (specifically MMAF) can significantly decrease the blastocyst formation rate which increases the average number of cycles required to achieve pregnancy.
_{Source: Long R, et al. (2024); Sun J P, et al. (2023); Tavalaee M, et al. (2023); Cheung S, et al. (2021); Hosseini S H, et al. (2021); Alukal J P and Lamb D J, (2008)}

Intracytoplasmic Morphologically selected Sperm Injection

Intracytoplasmic Morphologically selected Sperm Injection (IMSI) enables detailed morphological observation of individual sperm by increasing the optical resolution to 6000x magnification.

Experts originally hypothesised that this significant increase in magnification compared to ICSI (200x) could improve IVF outcomes for males with poor sperm morphology. However several studies fail to show a statistically significant improvement in clinical outcomes compared to ICSI for subfertile males.
_{Source: Boediono A, et al. (2021); Mangoli E, et al. (2019); Keskintepe L, et al. (2016)}

A recent time-lapse study however did confirm that IMSI significantly reduced the incidence of multinucleation, during embryo development. This suggests women with poor embryo quality overall may benefit by having their partner sperm selected via IMSI, although further studies are required to confirm this theory.
_{Source: Boediono A, et al. (2021)}

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