ABSTRACT
This case report presents a 36-year-old man with elongated sperm morphology, a specific type of teratozoospermia, associated with oxidative stress and deoxyribonucleic acid (DNA) damage. Six months of supplementation of L-carnitine, acetyl-L-carnitine, CoQ10, zinc, and vitamins, combined with lifestyle modifications enhanced sperm motility, morphology, and quality significantly. Posttreatment semen analysis showed improved concentration (13–20 million/mL), progressive motility (25%–40%), and normal morphology (2%–7%). The couple underwent intracytoplasmic morphologically selected sperm injection (IMSI), leading to successful fertilization, production of high-quality embryos, and confirmed pregnancy. This case illuminates the therapeutic potential of L-carnitine and acetyl-L-carnitine supplementation, in combination with IMSI, in treating male infertility associated with abnormal sperm morphology and improving outcomes of assisted reproductive technology.
KEYWORDS: Acetyl-l-carnitine, embryo, IMSI, infertility, l-carnitine, sperm, teratozoospermia
INTRODUCTION
Infertility is a pathological condition of the male or female reproductive system characterized by the inability to achieve pregnancy after at least 12 months of regular, unprotected sexual intercourse. The etiology of infertility may be attributed to male factors, female factors, or remain idiopathic.[1] It is a complex problem that can afflict both sexes because of contamination through environmental, biological, or lifestyle factors.[2] Male infertility is a common condition that contributes to approximately 50% of infertility cases worldwide.[3] One major factor affecting male infertility is abnormal sperm morphology, which plays a crucial role in infertility.[2] Sperm exhibits various types of abnormal morphology, one of which is elongated sperm—a condition known as teratozoospermia. According to the World Health Organization (WHO), teratozoospermia refers to sperm morphology below the lower reference limit.[3] In teratozoospermia, defects are found in the sperm’s head, midpiece, and tail. These abnormalities reduce the fertilization capacity.[4] This defect is often associated with oxidative stress, which compromises sperm DNA integrity, underscoring the importance of identifying effective treatment strategies.[5] Changes in lifestyle, combined with metabolic and nutritional improvements, play a significant role in improving sperm quality. L-carnitine is an amino acid derivative that plays an important role in the transport of fatty acids to the mitochondria and increases energy production required by sperms for normal functioning.[6] Similarly, acetyl-L-carnitine, a form of L-carnitine, has antioxidant properties and plays an essential role in protecting sperm from oxidative stress, which is an important contributor to male infertility.[7] L-carnitine and acetyl-L-carnitine have the potential to ameliorate abnormal sperm morphology, enhance spermatozoa motility, and improve overall fertility outcomes. This study assesses the role of L-carnitine and acetyl L-carnitine supplements in managing elongated morphology.[8]
CASE PRESENTATION
Patient information
An Indian couple visited the in vitro fertilization (IVF) center in Wardha. The ages of the male and female partners were 36 and 31 years, respectively. The individuals had been experiencing primary infertility for a duration of seven years. They subsequently provided informed consent to the healthcare facility.
Medical history
The couple had been attempting conception for seven years without success, and the etiology of their infertility remains undetermined. Multiple intrauterine insemination (IUI) cycles were conducted, all of which were unsuccessful. Additionally, a single in vitro fertilization (IVF) attempt also failed. Analysis of the male partner’s semen revealed abnormalities, particularly in sperm morphology, with a notable predominance of elongated spermatozoa. The male partner did not have any genetic or specific diseases; however, his history revealed that he consumes alcohol and has been smoking for the past 8 years. Conversely, the female partner’s hormonal profile was normal, and her reproductive system was also healthy.
Physical examination
Male partner
All the secondary sexual characteristics of the male partner were normal. There were no signs or symptoms of genital infections, varicocele, or any physical abnormalities.
Female partner
During the gynecologist’s examination, no problems or defects were found in the female partner. Her body mass index was within a healthy range, and no abnormalities were detected.
Investigation
The male partner underwent a series of diagnostic assessments, including hormonal profiling, which showed normal levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. Semen analysis was performed; the results are summarized in Table 1.
Table 1.
Semen analysis report (male partner)
| Parameter | Observed value | Normal range (WHO 2021) |
|---|---|---|
| Sperm concentration | 13 million/mL | ≥15 million/mL |
| Total sperm count | 22 million | ≥39 million/ejaculate |
| Volume | 2.5 mL | 1.5–5.0 mL |
| Motility (%) | 30% | >40% |
| Progressive motility | 25% | >32% |
| Non–progressive motility | 5 | <10% |
| Immotile sperm | 70% | <60% |
| Vitality (live sperm) % | 45% | ≥58% |
| Morphology (normal form) | 1% | ≥4% |
| Elongated heads | 40% | Rare |
Female partner underwent comprehensive diagnostic evaluation. Her hormonal profile, including anti-Müllerian hormone, follicle-stimulating hormone (FSH), and thyroid function, were all within the reference ranges. Imaging studies, such as ultrasound and hysterosalpingography, revealed normal uterine anatomy with patent fallopian tubes. No abnormalities were identified during the gynecological examination.
Treatment plan
Initially, lifestyle modification was done. The patient was advised to quit alcohol and smoking. Along with this, medical treatment was started, which was a combination of L-carnitine, acetyl-L-carnitine, coenzyme Q10, astaxanthin, ascorbic acid, zinc sulfate monohydrate, and tocopheryl acetate tablets for six months. During these six months, semen analysis was performed at three-month intervals. The patient improved significantly during these six months. The results are summarized in Table 2.
Table 2.
Pre- and post-treatment comparison of semen parameters
| Parameter | Pre- treatment | Post- treatment | Normal range (WHO 2021) |
|---|---|---|---|
| Sperm concentration | 13 million/mL | 20 million/mL | ≥15 million/mL |
| Volume | 2.5 mL | 3.5 mL | 1.5–5.0 mL |
| Morphology (normal form) | 2% | 7% | ≥4% |
| Progressive motility | 25% | 40% | >32% |
In this study, a graphical representation of the effect of supplementation on semen parameters is provided.
Sperm concentration, volume, morphology, and progressive motility were compared pre- and post-treatment and against the WHO normal range.
A significant improvement was observed across all evaluated parameters in this comparison.
The efficacy of the supplement was particularly evident during the post-treatment phase, as illustrated in Graph 1.
Graph 1.
Graphical representation of effect of L-carnitine and acetyl-L-carnitine supplementation on semen parameters
After six months, the female partner was subjected to oocyte retrieval. The sperms were then used with intracytoplasmic morphologically selected sperm injection (IMSI); this led to the production of good quality blastocysts [Figure 1]. These embryos were then frozen for later embryo transfer. Frozen embryo transfer in one cycle was planned. The treatment protocol for the endometrium involved metformin (500 mg), cabergoline (0.5 mg, twice a day) for managing hyperandrogenism, and low-dose exogenous estradiol at 4 mg/day. It was recommended to resume L-arginine supplementation starting one month after the oocyte pick-up (OPU) cycle to promote endometrial thickening by the third day of the menstrual cycle. The frozen embryo of the patient was thawed, and embryo transfer was performed using ultrasound guidance.
Figure 1.
A good-quality blastocyst was chosen for transfer
Follow up
The patient was advised to continue progesterone support and was guided on lifestyle adjustments and a nutritious diet. Beta human chorionic gonadotropin (beta-hCG) test was performed 15 days later, confirming pregnancy. Subsequently, sonography was done after 7 weeks, where fetal heartbeat and development were observed.
DISCUSSION
L-carnitine and acetyl-L-carnitine enhance sperm quality by modulating mitochondrial activity, thereby optimizing energy production and improving sperm motility. Both L-carnitine and acetyl-L-carnitine may mitigate oxidative stress by reducing reactive oxygen species (ROS) levels and lipid peroxidation, thereby preserving sperm integrity, maintaining DNA stability, and ensuring optimal plasma membrane functionality. Research also suggests that they improve sperm morphology, motility, and overall fertility outcomes, making them potential therapeutic agents in managing male infertility related to poor semen parameters.[9]
L-carnitine, essential for transporting fatty acids into mitochondria, enhances mitochondrial energy production and is vital for improving sperm morphology and motility. Acetyl-L-carnitine, with its superior bioavailability, complements L-carnitine’s effects by reducing oxidative stress, protecting sperm DNA integrity, and supporting mitochondrial function. Together, they synergistically promote sperm quality, enhancing motility and overall fertility, making them promising therapeutic agents for managing male infertility associated with impaired sperm parameters.[10]
L-carnitine and acetyl-L-carnitine supplementation has shown some benefits in terms of sperm quality and morphology in our case study. With a marked decrease in oxidative stress and an enhancement in mitochondrial functions, these substances reduce the presence of elongated sperms. This process facilitates the generation of structurally and functionally improved spermatozoa, thereby enhancing reproductive health and fertility outcomes. Consequently, these compounds hold potential as therapeutic agents for the management of male infertility.[11]
IMSI, utilizing high magnification, can select sperms with optimal morphology and reduced DNA fragmentation, thus highly improving fertilization outcomes. This process facilitates the generation of structurally and functionally improved spermatozoa, thereby enhancing reproductive health and fertility outcomes. Consequently, these compounds hold potential as therapeutic agents for the management of male infertility.[10]
A study by Lenzi et al.[11] demonstrated the effectiveness of combined L-carnitine and L-acetyl-carnitine therapy in improving sperm motility in infertile males with oligo-asthenic-teratozoospermia. The placebo-controlled trial revealed significant enhancements in total and forward sperm motility, particularly among patients with low motility levels. These findings support carnitine supplementation as a promising intervention to address male infertility, highlighting its role in mitochondrial function and protection against oxidative stress.
Nicotinamide adenine dinucleotide hydrogen NAD(H) and nicotinamide adenine dinucleotide phosphate NADP(H) play critical roles in maintaining cellular redox balance, which is vital for sperm function. Oxidative stress, characterized by excessive ROS, disrupts this balance, impairing sperm motility, morphology, and DNA integrity. L-carnitine and acetyl-L-carnitine enhance mitochondrial activity and energy metabolism by restoring the NAD(H)/NADP(H) ratio, thereby mitigating ROS-induced damage. Their therapeutic potential in managing oxidative stress-related male infertility underscores the importance of targeting mitochondrial function to improve sperm quality and fertilization outcomes.[12]
This case report shows that L-carnitine and acetyl-L carnitine supplementation could improve the sperm quality of males having abnormal morphology, including elongated forms. The patient exhibited improved sperm motility, suggesting that Intracytoplasmic Morphologically Selected Sperm Injection (IMSI) could be a promising approach for managing cases of assisted reproductive technology (ART) failure.[13]
Future studies should determine the long-term effects and optimal dosage of L-carnitine and acetyl-L-carnitine supplementation in the management of male infertility. Further large-scale randomized controlled trials will be necessary to confirm their efficacy in diverse populations and explore their impact on DNA fragmentation and live birth rates. Further research into the synergistic effects of these supplements with other antioxidants or ART techniques, such as IMSI, will be necessary for obtaining deeper insights. Further research on the molecular mechanisms of these supplements will enhance their clinical application by elucidating their role in mitigating oxidative stress and optimizing mitochondrial function.
CONCLUSION
In conclusion, this case report demonstrates the promising role of L-carnitine and acetyl-L-carnitine supplementation in improving sperm quality, particularly in men with abnormal sperm morphology such as elongated sperms. The treatment, coupled with lifestyle modifications, resulted in a significant enhancement of sperm motility, morphology, and overall semen parameters. The use of IMSI further improved fertilization success by selecting sperms with optimal morphology and DNA integrity. This combination approach contributed to the successful pregnancy of the couple, emphasizing the therapeutic potential of L-carnitine and acetyl-L-carnitine in male infertility, particularly in cases of teratozoospermia and ART failure. Thus, supplementation with these compounds, in combination with advanced ART techniques such as IMSI, may offer a valuable strategy in the management of male infertility associated with poor sperm morphology and oxidative stress.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Conflicts of interest
There are no conflicts of interest.
Funding Statement
Nil.
REFERENCES
- 1.Starc A, Trampuš M, Jukić DP, Rotim C, Jukić T, Mivšek AP. Infertility and sexual dysfunctions: A systematic literature review. Acta Clin Croat. 2019;58:508–15. doi: 10.20471/acc.2019.58.03.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Moretti E, Signorini C, Noto D, Corsaro R, Collodel G. The relevance of sperm morphology in male infertility. Front Reprod Health. 2022;4:945351. doi: 10.3389/frph.2022.945351. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Dehghanpour F, Tabibnejad N, Fesahat F, Yazdinejad F, Talebi AR. Evaluation of sperm protamine deficiency and apoptosis in infertile men with idiopathic teratozoospermia. Clin Exp Reprod Med. 2017;44:73. doi: 10.5653/cerm.2017.44.2.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Meyer-Ficca ML, Ihara M, Bader JJ, Leu NA, Beneke S, Meyer RG. Spermatid head elongation with normal nuclear shaping requires ADP-ribosyltransferase PARP11 (ARTD11) in Mice1. Biol Reprod. 2015;92:80. doi: 10.1095/biolreprod.114.123661. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Aliabadi E, Soleimani Mehranjani M, Borzoei Z, Talaei-Khozani T, Mirkhani H, Tabesh H. Effects of L-carnitine and L-acetyl-carnitine on testicular sperm motility and chromatin quality. Iran J Reprod Med. 2012;10:77–82. [PMC free article] [PubMed] [Google Scholar]
- 6.Agarwal A, Tvrda E, Sharma R. Relationship amongst teratozoospermia, seminal oxidative stress and male infertility. Reprod Biol Endocrinol. 2014;12:45. doi: 10.1186/1477-7827-12-45. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Mateus FG, Moreira S, Martins AD, Oliveira PF, Alves MG, Pereira MDL. L-carnitine and male fertility: Is supplementation beneficial? J Clin Med. 2023;12:5796. doi: 10.3390/jcm12185796. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Lenzi A, Sgrò P, Salacone P, Paoli D, Gilio B, Lombardo F, et al. Aplacebo-controlled double-blind randomized trial of the use of combined l-carnitine and l-acetyl-carnitine treatment in men with asthenozoospermia. Fertil Steril. 2004;81:1578–84. doi: 10.1016/j.fertnstert.2003.10.034. [DOI] [PubMed] [Google Scholar]
- 9.Aitken RJ, Drevet JR, Moazamian A, Gharagozloo P. Male infertility and oxidative stress: A focus on the underlying mechanisms. Antioxidants (Basel) 2022;11:306. doi: 10.3390/antiox11020306. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Khaw SC, Wong ZZ, Anderson R, Martins Da Silva S. L-carnitine and l-acetylcarnitine supplementation for idiopathic male infertility. Reproduct Fertil. 2020;1:67–81. doi: 10.1530/RAF-20-0037. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Lenzi A, Sgrò P, Salacone P, Paoli D, Gilio B, Lombardo F, et al. Aplacebo-controlled double-blind randomized trial of the use of combined l-carnitine and l-acetyl-carnitine treatment in men with asthenozoospermia. Fertil Steril. 2004;81:1578–84. doi: 10.1016/j.fertnstert.2003.10.034. [DOI] [PubMed] [Google Scholar]
- 12.Tonazzi A, Giangregorio N, Console L, Palmieri F, Indiveri C. The mitochondrial carnitine acyl-carnitine carrier (SLC25A20): Molecular mechanisms of transport, role in redox sensing and interaction with drugs. Biomolecules. 2021;11:521. doi: 10.3390/biom11040521. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Xiao W, Wang RS, Handy DE, Loscalzo J. NAD(H) and NADP(H) redox couples and cellular energy metabolism. Antioxid Redox Signal. 2018;28:251–72. doi: 10.1089/ars.2017.7216. [DOI] [PMC free article] [PubMed] [Google Scholar]