'Intracytoplasmic sperm injection (ICSI) paradox' and 'andrological ignorance': AI in the era of fourth industrial revolution to navigate the blind spots.

The quandary known as the Intracytoplasmic Sperm Injection (ICSI) paradox is found at the juncture of Assisted Reproductive Technology (ART) and 'andrological ignorance' - a term coined to denote the undervalued treatment and comprehension of male infertility. The prevalent use of ICSI as a solution for severe male infertility, despite its potential to propagate genetically defective sperm, consequently posing a threat to progeny health, illuminates this paradox. We posit that the meteoric rise in Industrial Revolution 4.0 (IR 4.0) and Artificial Intelligence (AI) technologies holds the potential for a transformative shift in addressing male infertility, specifically by mitigating the limitations engendered by 'andrological ignorance.' We advocate for the urgent need to transcend andrological ignorance, envisaging AI as a cornerstone in the precise diagnosis and treatment of the root causes of male infertility. This approach also incorporates the identification of potential genetic defects in descendants, the establishment of knowledge platforms dedicated to male reproductive health, and the optimization of therapeutic outcomes. Our hypothesis suggests that the assimilation of AI could streamline ICSI implementation, leading to an overall enhancement in the realm of male fertility treatments. However, it is essential to conduct further investigations to substantiate the efficacy of AI applications in a clinical setting. This article emphasizes the significance of harnessing AI technologies to optimize patient outcomes in the fast-paced domain of reproductive medicine, thereby fostering the well-being of upcoming generations.

Oxidative stress affects sperm health and fertility-Time to apply facts learned at the bench to help the patient: Lessons for busy clinicians.

Background: Increased oxidative stress (OS), resulting from the delicate balance between reactive oxygen species (ROS) production and antioxidant defense, is closely linked to sperm abnormalities and male subfertility. Elevated ROS levels particularly affect sperm quality. The vulnerability of spermatozoa to ROS is due to the absence of DNA repair mechanisms and the high presence of polyunsaturated fatty acids in their membranes. Methods: This article updates and advances our understanding of the molecular damage caused by OS in spermatozoa, including lipid peroxidation, DNA damage, motility, and functionality. Additionally, the review discusses the challenges in diagnosing OS in semen and recommends accurate and sensitive testing methods. Case studies are utilized to demonstrate the effective management of male infertility caused by OS. Main findings: Highlighting the need to bridge the gap between research and clinical practice, this review suggests strategies for clinicians, such as lifestyle and dietary changes and antioxidant therapies. The review emphasizes lifestyle modifications and personalized care as effective strategies in managing male infertility caused by OS. Conclusion: This review calls for early detection and intervention and interdisciplinary collaboration to improve patient care in male infertility cases related to increased OS.

Optimization of estrogen dosage for uterine receptivity for implantation in post-coital bilaterally ovariectomized mice.

Estrogens and progesterone, in unison and/or separately, synchronize the distinct events of blastocyst development, uterine priming and receptivity induction for implantation. In contrast to high implantation failure rates, the mechanistic concepts regarding the uterine receptivity for implantation still remain elusive. The present study aims to define the minimum estradiol (E2) dose to induce uterine receptivity for successful implantation in post-coitus bilaterally ovariectomized (BLO) progesterone-primed uterus of mice. Post-coital sperm-positive adult female mice were divided into two groups. In both the groups, delayed implantation was induced by BLO on post-coitus Day 4 (D4). Group 1 received 2 mg of progesterone (P4) from D5 until sacrifice, and E2 injection of 3.0, 10.0, 25.0 and 50.0 ng on D7. On D8, all mice of this group were sacrificed except the mice that received second dose of 25.0 ng of E2 on D8 and were sacrificed on D9. Group 2 followed the same doses, but were given simultaneously on D4, and sacrificed on D5. The mice that received second doses of 25.0 ng E2 were sacrificed on D6. The minimum dose of E2 required to induce uterine receptivity for implantation is a single dose of 50.0 ng E2. The uterus remained refractory following short receptive period at E2 doses lower than 50.0 ng, which is just sufficient to establish desired uterine receptivity. However, repeated administration of sub-threshold doses of 25.0 ng of E2 could also not effectively sustain uterine receptivity towards successful implantation.

Oxidant-Sensitive Inflammatory Pathways and Male Reproductive Functions.

Male component is the major contributing factor in over half of all cases of infertility, with over 25% of infertile males having no recognised underlying cause of infertility. In around 40-50% of male infertility cases, oxidative stress (OS)-related processes have been found to be responsible for fertility impairment. Inflammation is a major stress signal leading to OS. Redox imbalance occurs when endogenous antioxidant network fails to curb the excess generation of reactive oxygen species (ROS), leading to activation of stress-sensitive intracellular signalling pathways directed to cellular damage. Oxidant-sensitive-inflammatory pathways are intricate vicious intracellular networking loops that initiate and exaggerate cellular damage, including chronic impact on male reproductive tissues. These mechanisms, however, are poorly known in connection to male reproductive abnormalities. Thus, the goal of this chapter is to explain the oxidant-sensitive-inflammatory pathways in male reproductive organs in a succinct manner, as well as their potential influence on male fertility.

Oxidative Stress and Idiopathic Male Infertility.

Idiopathic male infertility (IMI) refers to the condition where semen quality declines, but exact causatives are not identified. This occurs in almost 30-40% of infertile men. Traditional semen analyses are extensively used for determining semen quality, but these bear critical shortcomings such as poor reproducibility, subjectivity, and reduced prediction of fertility. Oxidative stress (OS) has been identified as the core common mechanism by which various endogenous and exogenous factors may induce IMI. Male oxidative stress infertility (MOSI) is a term used to describe infertile males with abnormal semen parameters and OS. For the treatment of MOSI, antioxidants are mostly used which counteract OS and improve sperm parameters with appropriate combinations, dosage, and duration. Diagnosis and management of male infertility have witnessed a substantial improvement with the advent in the omics technologies that address at genetic, molecular, and cellular levels. Incorporation of oxidation-reduction potential (ORP) can be a useful clinical biomarker for MOSI. Moreover, various modulations of male fertility status can be achieved via stem cell and next-generation sequencing (NGS) technologies. However, several challenges must be overcome before the advanced techniques can be utilized to address IMI, including ethical and religious considerations, as well as the possibility of genetic abnormalities. Considering the importance of robust understanding of IMI, its diagnosis, and possible advents in management, the present article reviews and updates the available information in this realm, emphasizes various facets of IMI, role of OS in its pathophysiology, and discusses the novel concept of MOSI with a focus on its diagnostic and therapeutic aspects.

Reductive Stress and Male Infertility.

Male infertility research and clinical advances had vast progress in the last few decades. Strong research evidence underpinned the concepts of oxidative stress (OS)-mediated male reproductive disruptions, which bear answers to several cases of idiopathic male infertility. Antioxidant treatment held the prime solution for OS-mediated male infertility. But excess use of antioxidants is challenged by the research breakthrough that reductive stress also predisposes to male infertility, resolutely instituting that any biological extremes of the redox spectrum are deleterious to male fertility. Superfluity of reducing agents may hinder essential oxidation mechanisms, affecting physiological homeostasis. These mechanisms need to be explicated and updated time and again to identify the fine thread between OS-mediated male infertility treatment and induction of reductive stress. This chapter thus presents the evidence-based concepts pertaining to the antioxidants actions to combat OS-induced male infertility, the mechanism of induction of reductive stress and its impact on male reproduction.

Arsenic-Induced Sex Hormone Disruption: An Insight into Male Infertility.

Arsenic (As) is one of the most potent natural as well as anthropogenic metalloid toxicants that have various implications in the everyday life of humans. It is found in several chemical forms such as inorganic salt, organic salt, and arsine (gaseous form). Although it is mostly released via natural causes, there are many ways through which humans come in contact with As. Drinking water contamination by As is one of the major health concerns in various parts of the world. Arsenic exposure has the ability to induce adverse health effects including reproductive problems. Globally, around 15% of the couples are affected with infertility, of which about 20-30% are attributed to the male factor. Arsenic affects the normal development and function of sperm cells, tissue organization of the gonads, and also the sex hormone parameters. Stress induction is one of the implications of As exposure. Excessive stress leads to the release of glucocorticoids, which impact the oxidative balance in the body leading to overproduction of reactive oxygen species (ROS). This may in turn result in oxidative stress (OS) ultimately interfering with normal sperm and hormonal parameters. This study deals with As-induced OS and its association with sex hormone disruption as well as its effect on sperm and semen quality.

Reactive Nitrogen Species and Male Reproduction: Physiological and Pathological Aspects.

Reactive nitrogen species (RNS), like reactive oxygen species (ROS), are useful for sustaining reproductive processes such as cell signaling, the regulation of hormonal biosynthesis, sperm capacitation, hyperactivation, and acrosome reaction. However, endogenous levels of RNS beyond physiological limits can impair fertility by disrupting testicular functions, reducing gonadotropin production, and compromising semen quality. Excessive RNS levels cause a variety of abnormalities in germ cells and gametes, particularly in the membranes and deoxyribonucleic acid (DNA), and severely impair the maturation and fertilization processes. Cell fragmentation and developmental blockage, usually at the two-cell stage, are also connected with imbalanced redox status of the embryo during its early developmental stage. Since high RNS levels are closely linked to male infertility and conventional semen analyses are not reliable predictors of the assisted reproductive technology (ART) outcomes for such infertility cases, it is critical to develop novel ways of assessing and treating oxidative and/or nitrosative stress-mediated male infertility. This review aims to explicate the physiological and pathological roles of RNS and their relationship with male reproduction.

N-acetyl cysteine as a potential regulator of SARS-CoV-2-induced male reproductive disruptions.

Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causing the coronavirus disease 2019 (COVID-19), has shown its persistent pandemic strength. This viral infectivity, kinetics, and the mechanisms of its actions in human body are still not completely understood. In addition, the infectivity and COVID-19 severity reportedly differ with patient's gender with men being more susceptible to the disease. Thus, different studies have also suggested the adverse impact of COVID-19 on male reproductive functions, mainly emphasizing on high expressions of angiotensin-converting enzyme 2 (ACE2) in the testes that allows the viral entry into the cells. Main body: The N-acetylcysteine (NAC), a potent therapeutic agent of COVID-19, may be effective in reducing the impairing impacts of this disease on male reproductive functions. NAC acts as mucolytic agent by reducing sulfide bonds in the cross-linked glycoprotein matrix in mucus owing to its free sulfhydryl group. Since NAC also breaks the viral disulfide bonds required for the host cell invasion, it may help to prevent direct SARS-CoV-2 invasion into the testicular cells as well. NAC also acts as a potent anti-inflammatory and antioxidant, directly scavenging reactive oxygen species (ROS) and regulating the redox state by maintaining the thiol pool being a precursor of cysteine (an essential substrate for glutathione synthesis). Since it is suggested that male reproductive impairment in COVID-19 patient may be caused by secondary immune responses owing to systemic inflammation and OS, the anti-inflammatory and antioxidant properties of NAC explained above may attribute in protecting the male reproduction functions from these COVID-19-mediated damages. Conclusion: This article explains the mechanisms how NAC treatment for COVID-19 may prevent the infection-mediated disruptions in male reproduction.

The Role of Nitric Oxide on Male and Female Reproduction.

Nitric oxide (NO), a reactive nitrogen species, is a molecule of high physiological as well as pathological importance. Physiological mechanisms mediated by NO mainly include angiogenesis, growth, puberty and senescence. NO has vital roles in normal reproduction, including steroidogenesis, gametogenesis and the regulation of germ-cell apoptosis. In females, NO stimulates an inflammatory cascade to induce ovulation, decreases steroidogenesis in luteal and granulosa cells, and acts as a paracrine factor to mediate reproductive cycles and implantation. In males, NO is a key player for steroidogenesis, erectile functions, sperm capacitation and acrosome reaction. Moreover, NO is also a regulator of Sertoli cell-germ cell interaction and maintenance of the blood-testis barrier. In pathological conditions such as infections, increased nitric oxide synthase (NOS) activities stimulate the excessive synthesis of NO which acts as a proinflammatory mediator inducing oxidative stress (OS), which is detrimental to reproductive functions in both males and females. During impregnation, the overproduction of NO results in uterine epithelial cell inflammation and immune rejection of implantation. Excessive NO synthesis disrupts gonadal functions, and induces germ cell apoptosis and oxidative damage to the germ cells. This review elucidates how the differences in NO expression levels account for its beneficial and adverse impacts upon male and female fertility.

Obesity and male infertility: Mechanisms and management.

Obesity is considered a global health problem affecting more than a third of the population. Complications of obesity include cardiovascular diseases, type 2 diabetes mellitus, malignancy (including prostatic cancer), neurodegeneration and accelerated ageing. In males, these further include erectile dysfunction, poor semen quality and subclinical prostatitis. Although poorly understood, important mediators of obesity that may influence the male reproductive system include hyperinsulinemia, hyperleptinemia, chronic inflammation and oxidative stress. Obesity is known to disrupt male fertility and the reproduction potential, particularly through alteration in the hypothalamic-pituitary-gonadal axis, disruption of testicular steroidogenesis and metabolic dysregulation, including insulin, cytokines and adipokines. Importantly, obesity and its underlying mediators result in a negative impact on semen parameters, including sperm concentration, motility, viability and normal morphology. Moreover, obesity inhibits chromatin condensation, DNA fragmentation, increases apoptosis and epigenetic changes that can be transferred to the offspring. This review discusses the impact of obesity on the male reproductive system and fertility, including associated mechanisms. Furthermore, weight management strategies, lifestyle changes, prescription medication, and complementary and alternative medicine in the management of obesity-induced subfertility is discussed.

An online educational model in andrology for student training in the art of scientific writing in the COVID-19 pandemic.

In 2020, the COVID-19 pandemic led to the suspension of the annual Summer Internship at the American Center for Reproductive Medicine (ACRM). To transit it into an online format, an inaugural 6-week 2020 ACRM Online Mentorship Program was developed focusing on five core pillars of andrology research: scientific writing, scientific methodology, plagiarism understanding, soft skills development and mentee basic andrology knowledge. This study aims to determine mentee developmental outcomes based on student surveys and discuss these within the context of the relevant teaching and learning methodology. The mentorship was structured around scientific writing projects established by the team using a student-centred approach, with one-on-one expert mentorship through weekly formative assessments. Furthermore, weekly online meetings were conducted, including expert lectures, formative assessments and social engagement. Data were collected through final assessments and mentee surveys on mentorship outcomes. Results show that mentees (n = 28) reported a significant (p < .0001) improvement in all criteria related to the five core pillars. These results illustrate that the aims of the online mentorship program were achieved through a unique and adaptive online educational model and that our model has demonstrated its effectiveness as an innovative structured educational experience through the COVID-19 crisis.

Oxidative Stress, Testicular Inflammatory Pathways, and Male Reproduction.

Inflammation is among the core causatives of male infertility. Despite male infertility being a serious global issue, "bits and pieces" of its complex etiopathology still remain missing. During inflammation, levels of proinflammatory mediators in the male reproductive tract are greater than usual. According to epidemiological research, in numerous cases of male infertility, patients suffer from acute or chronic inflammation of the genitourinary tract which typically occurs without symptoms. Inflammatory responses in the male genital system are inextricably linked to oxidative stress (OS). OS is detrimental to male fertility parameters as it causes oxidative damage to reproductive cells and intracellular components. Multifarious male infertility causative factors pave the way for impairing male reproductive functions via the common mechanisms of OS and inflammation, both of which are interlinked pathophysiological processes, and the occurrence of any one of them induces the other. Both processes may be simultaneously found in the pathogenesis of male infertility. Thus, the present article aims to explain the role of inflammation and OS in male infertility in detail, as well as to show the mechanistic pathways that link causative factors of male reproductive tract inflammation, OS induction, and oxidant-sensitive cellular cascades leading to male infertility.

SARS-CoV-2 infection and human semen: possible modes of contamination and transmission.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has turned into a global pandemic with multitudinous health impacts. MAIN BODY: In light of the higher vulnerability of men to COVID-19 than women, there is rising concerns on the impact of SARS-CoV-2 infection on male fertility and possibilities of seminal contamination and transmission. The pandemic has attributed to the brief suspension of many fertility clinics and pathology laboratories, though many remained functional. Few reports reflect that SARS-CoV-2 can contaminate the semen of COVID-19 patients as well as that of recovering patients. The viral invasion into the testis may be due to the disrupted anatomical barriers of the testis by the inflammatory responses, and the persistence of the virus in the semen may be facilitated by the testicular immune privilege. Since SARS-CoV-2 is an enveloped RNA virus, it is also theoretically possible that this virus can remain viable in the semen samples even after cryopreservation with liquid nitrogen. CONCLUSION: The present review emphasizes the possibilities of seminal dissemination of SARS-CoV-2 and thereby the chances of its sexual transmission. These perceptions and predictions are to facilitate immediate necessary actions to improvise the standard precautionary procedures for laboratory practices, including semen analysis or processing the semen sample for fertility treatments.

Staphylococcal infections and infertility: mechanisms and management.

Infertility is a subject of worldwide concern as it affects approximately 15% of couples. Among the prime contributors of infertility, urogenital bacterial infections have lately gained much clinical importance. Staphylococcal species are commensal bacteria and major human pathogens mediating an array of reproductive tract infections. Emerging evidences are 'bit by bit' revealing the mechanisms by which Staphylococci strategically disrupt normal reproductive functions. Staphylococcal species can directly or through hematogenous routes can invade the reproductive tissues. In the testicular cells, epididymis as well as in various compartments of female reproductive tracts, the pathogen recognition receptors, toll-like receptors (TLRs), can recognize the pathogen-associated molecular patterns on the Staphylococci and thereby activate inflammatory signalling pathways. These elicit pro-inflammatory mediators trigger other immune cells to infiltrate and release further inflammatory agents and reactive oxygen species (ROS). Adaptive immune responses may intensify the inflammation-induced reproductive tissue damage, particularly via activation of T-helper (Th) cells, Th1 and Th17 by the innate components or by staphylococcal exotoxins. Staphylococcal surface factors binding with sperm membrane proteins can directly impair sperm functions. Although Staphylococci, being one of the most virulent bacterial species, are major contributors in infection-induced infertility in both males and females, the mechanisms of their operations remain under-discussed. The present review aims to provide a comprehensive perception of the possible mechanisms of staphylococcal infection-induced male and female infertility and aid potential interventions to address the lack of competent therapeutic measures for staphylococcal infection-induced infertility.

Geographical differences in semen characteristics: Comparing semen parameters of infertile men of the United States and Iraq.

The declining trend of male fecundity is a major global health and social concern. Among numerous other confounding factors, variations in male fertility parameters in different regions have repeatedly been suggested to be influenced by geographic locations. The impact of overall lifestyle, behavioural patterns, ethnicity, work stress and associated factors upon health differ greatly between developed and developing countries. These factors, individually or in combination, affect male reproductive functions ensuing the discrepancies in semen qualities in connection with geographic variations. However, reports comparing semen characteristics between developed and developing countries are sparse. The present study finds its novelty in presenting a comparison in semen parameters of infertile men in the United States (n = 76) that fairly represents the population of a highly developed region and Iraq (n = 102), the representative of male populations of a developing region. Samples were collected and analysed according to WHO (WHO laboratory manual for the examination and processing of human semen, WHO; 2010) criteria by means of the Mann-Whitney test. The US population demonstrated lower sperm concentration, total count, and total and progressive sperm motility with a higher seminal total antioxidant capacity (TAC) as compared to the Iraqi population. This report encourages further investigations concerning the confounding factors leading to such alterations in semen qualities between these two geographic areas.

Sociodemographic factors associated with semen quality among Malaysian men attending fertility clinic.

The worldwide declining trend in male fertility has been a steady concern since the past few decades. Male infertility reportedly accounts for half of the overall infertility cases in the world. Despite the evidences of reduced fertility rates in Malaysia in the recent years, there is lack of interventions regarding the reproductive parameters in Malaysian men. Complexity in determining the underlying causatives in most of the male subfertility and infertility cases limits the scope of management. The sociodemographic impacts upon overall health as well as on reproductive health of men are undeniable. The present study has analysed the data collected from patients' records in the Fertility Clinic, International Islamic University Malaysia (IIUM), from the January 2009 until December 2018. A total of 300 male patients were included in the study and were categorised according to their seminal fluid analysis (SFA) records. The sociodemographic characteristics for each subject were analysed. The results presented significant correlations among essential sociodemographic factors, such as educational attainment, marital duration as well as the age of wife, with the levels of semen abnormalities in the subjects. The study thereby unleashes scope for further investigations focusing upon the demographic factors for better insights to ameliorate male reproductive health in the Malaysian population.

Oxidative stress-induced alterations in seminal plasma antioxidants: Is there any association with keap1 gene methylation in human spermatozoa?

Kelch-like ECH-associated protein 1 (keap1)-nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway is one of the master regulators of cellular defence against oxidative stress. Epigenetic alterations like hypermethylation of keap1 gene impair keap1-Nrf2 system in several oxidative stress-associated diseases. The objective of this study was to evaluate the epigenetic status of keap1 in sperm DNA of normozoospermic subjects, having different levels of reactive oxygen species (ROS) in seminal plasma. Semen samples were obtained from 151 apparently healthy male partners of couples who attended the Avicenna infertility clinic. Samples were categorised into four groups according to their ROS levels: group A (n = 39, ROS < 20 RLU/s per 106 spermatozoa), group B (n = 38, 20 ≤ ROS < 40 RLU/s per 106 spermatozoa), group C (n = 31, 40 ≤ ROS < 60 RLU/s per 106 spermatozoa) and group D; (n = 43, ROS ≥ 60 RLU/s per 106 spermatozoa). Keap1 methylation status was assessed using methylation-specific PCR along with seminal total antioxidant capacity. The results showed no significant alterations in keap1 methylation in any groups, whereas the total antioxidant capacity enhanced with increasing levels of ROS exposure. These results indicate that keap1 was not methylated during ROS elevation and oxidative stress, suggesting that the cells have adopted other mechanisms to elevate antioxidant level.

Reactive oxygen species-induced alterations in H19-Igf2 methylation patterns, seminal plasma metabolites, and semen quality.

PURPOSE: This study was conducted in order to investigate the effects of reactive oxygen species (ROS) levels on the seminal plasma (SP) metabolite milieu and sperm dysfunction. METHODS: Semen specimens of 151 normozoospermic men were analyzed for ROS by chemiluminescence and classified according to seminal ROS levels [in relative light units (RLU)/s/106 sperm]: group 1 (n = 39): low (ROS < 20), group 2 (n = 38): mild (20 ≤ ROS < 40), group 3 (n = 31): moderate (40 ≤ ROS < 60), and group 4 (n = 43): high (ROS ≥ 60). A comprehensive analysis of SP and semen parameters, including conventional semen characteristics, measurement of total antioxidant capacity (TAC), sperm DNA fragmentation index (DFI), chromatin maturation index (CMI), H19-Igf2 methylation status, and untargeted seminal metabolic profiling using nuclear magnetic resonance spectroscopy (1H-NMR), was carried out. RESULT(S): The methylation status of H19 and Igf2 was significantly different in specimens with high ROS (P < 0.005). Metabolic fingerprinting of these SP samples showed upregulation of trimethylamine N-oxide (P < 0.001) and downregulations of tryptophan (P < 0.05) and tyrosine/tyrosol (P < 0.01). High ROS significantly reduced total sperm motility (P < 0.05), sperm concentration (P < 0.001), and seminal TAC (P < 0.001) but increased CMI and DFI (P < 0.005). ROS levels have a positive correlation with Igf2 methylation (r = 0.19, P < 0.05), DFI (r = 0.40, P < 0.001), CMI (r = 0.39, P < 0.001), and trimethylamine N-oxide (r = 0.45, P < 0.05) and a negative correlation with H19 methylation (r = - 0.20, P < 0.05), tryptophan (r = - 0.45, P < 0.05), sperm motility (r = - 0.20, P < 0.05), sperm viability (r = - 0.23, P < 0.01), and sperm concentration (r = - 0.30, P < 0.001). CONCLUSION(S): Results showed significant correlation between ROS levels and H19-Igf2 gene methylation as well as semen parameters. These findings are critical to identify idiopathic male infertility and its management through assisted reproduction technology (ART).

Role of L-carnitine in female infertility.

BACKGROUND: L-carnitine (LC), and its acetylated form, acetyl L-carnitine (ALC), have immense functional capabilities to regulate the oxidative and metabolic status of the female reproductive system. The vulnerability of this system to free radicals demand for advanced strategies to combat them. For this purpose, the 'quasi vitamins' LC and ALC can be used either individually, or in combination with each other or with other antioxidants. MAIN BODY: This review (a) summarizes the effects of carnitines on female fertility along with the findings from various in vivo and in vitro studies involving human, animal and assisted reproductive technology, and (b) proposes their mechanism of actions in improving female fertility through their integrated actions on reducing cellular stress, maintaining hormonal balance and enhancing energy production. They reportedly aid ß-oxidation in oocytes, maintain its cell membrane stability by acetylation of phospholipids and amphiphilic actions, prevent free radical-induced DNA damage and also stabilize acetyl Co-A/Co-A ratio for adequate acetyl storage as energy supply to maintain the robustness of reproductive cells. CONCLUSION: While both LC and ALC have their applications in improving female fertility, ALC is preferred for its better antioxidant properties and LC for amelioration of energy supply to the cells. These beneficial effects show great promise in its application as a treatment option for women facing infertility disorders.