Nandkumar Shinde College of Pharmacy, Chatrapati Sambhajinagar, Maharastra, India
Infertility, affecting millions of couples globally, remains a complex and multifactorial issue with both male and female contributors. Recent advancements in artificial intelligence [AI] offer new hope in revolutionizing infertility diagnosis and treatment. AI's ability to analyze large datasets, identify patterns, and provide predictive insights has paved the way for personalized, more effective fertility care. This review explores the transformative role of AI in managing infertility, including its applications in diagnostic imaging, predictive analytics, genetic testing, and personalized treatment planning. AI also enhances assisted reproductive technologies [ART], such as in vitro fertilization [IVF], by improving embryo and sperm selection, as well as optimizing treatment protocols. Despite its promising potential, AI in fertility medicine raises important ethical and practical challenges, including data privacy, algorithmic biases, and the need for rigorous clinical validation. The review calls for more research, standardized practices, and ethical frameworks to ensure the responsible integration of AI into reproductive healthcare.
Infertility in humans
Infertility in humans is defined as the inability of a couple to conceive naturally after one year of regular, unprotected intercourse.[1] This condition affects both men and women, but the causes, risk factors, and biological mechanisms can vary between genders. Male infertility often arises from issues with sperm production, motility, or morphology, while female infertility is frequently linked to ovulation disorders, tubal blockages, or uterine abnormalities[2] In many cases, infertility has multifactorial origins, where lifestyle factors, genetics, environmental influences, and underlying medical conditions all play contributing roles[3] Globally, infertility is a prevalent concern, impacting an estimated 8-12% of couples of reproductive age, with rates increasing in recent decades due to factors such as delayed childbearing, lifestyle changes, and higher exposure to environmental toxins.[4,5] As the demand for innovative reproductive solutions grows, advancements in reproductive medicine, such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), have provided substantial relief for many couples. However, these interventions are complex, costly, and not always successful on the first attempt, underscoring the need for further optimization in treatment approaches.[6] In this context, artificial intelligence (AI) has emerged as a transformative tool, offering new capabilities for diagnosing, treating, and managing infertility. AI algorithms can analyze vast datasets to identify patterns in fertility biomarkers, optimize embryo selection in IVF, and even personalize treatment plans by predicting individual success rates based on various biological factors.[7] By integrating AI into reproductive health, clinicians can increase the efficiency and accuracy of infertility treatment, making it a promising frontier in addressing this global health issue.[8]
Causes and Risk Factors
Infertility in humans arises from a complex interplay of biological, genetic, lifestyle, and environmental factors. Among the most common causes are hormonal imbalances, which can affect both men and women. For women, hormonal disruptions in the hypothalamus-pituitary- ovarian axis can prevent ovulation or result in inadequate endometrial preparation for implantation, as seen in conditions like polycystic ovary syndrome [PCOS] and hyperprolactinemia.[9] In men, low levels of testosterone or abnormal levels of follicle- stimulating hormone [FSH] can impair sperm production and function.[10] Genetic factors also contribute to infertility, with chromosomal abnormalities and gene mutations affecting reproductive capacity in both sexes. Examples include Y-chromosome microdeletions in males and Turner syndrome in females.[11] Lifestyle influences such as high stress, smoking, excessive alcohol intake, obesity, and poor diet can also impact fertility. Studies show that excessive body weight disrupts hormonal balance and can lead to anovulation in women, while high body fat in men is associated with lower sperm quality.[12] Environmental exposures, such as exposure to endocrine-disrupting chemicals (EDCs) like phthalates, bisphenol A (BPA), and pesticides, are increasingly recognized as significant contributors to infertility. These chemicals can interfere with hormone functions, impacting reproductive health and potentially leading to decreased fertility in both genders.[13]
Current Diagnostic Techniques
A range of diagnostic techniques is available to identify the underlying causes of infertility, often starting with hormone assays that measure levels of key reproductive hormones. For women, levels of FSH, luteinizing hormone (LH), estrogen, and anti-Müllerian hormone (AMH) are assessed to determine ovarian reserve and function.[14] In men, testosterone, FSH, and LH levels are evaluated to assess spermatogenesis. Imaging techniques, such as transvaginal ultrasound in women, are used to visualize the ovaries, uterus, and fallopian tubes, helping detect abnormalities such as polyps, fibroids, and cysts. Advanced imaging like hysterosalpingography (HSG) and laparoscopy are employed for detailed evaluation of the reproductive organs and to confirm tubal patency.[15] Genetic testing is increasingly recommended, particularly for individuals with a family history of reproductive issues. Genetic tests can identify chromosomal abnormalities and single-gene disorders that might impair fertility or increase the risk of miscarriage. For men, sperm analysis remains a cornerstone of fertility diagnosis, assessing factors like sperm count, motility, and morphology, which are critical indicators of male fertility potential.[16]
Traditional Treatments
Infertility treatments aim to address underlying causes and enhance the chances of conception. Medications are often the first-line treatment, especially for hormonal imbalances. Clomiphene citrate, for example, is used to stimulate ovulation in women, while men may be prescribed medications to address low testosterone levels.[17] Intrauterine insemination (IUI) is a common procedure for couples with unexplained infertility or mild male factor infertility, where washed sperm are directly introduced into the uterus to facilitate fertilization. In vitro fertilization (IVF) is another widely used treatment, especially for couples who have not succeeded with less invasive methods. During IVF, eggs are fertilized with sperm outside the body, and viable embryos are then implanted into the uterus. IVF has proven particularly effective for patients with tubal blockages, endometriosis, or severe male factor infertility.[18] Surgery is also an option when anatomical abnormalities, such as uterine fibroids or blocked fallopian tubes, are present, allowing for correction of these structural issues to improve fertility outcomes.[19]
Applications of AI in Infertility Diagnosis
Artificial intelligence has shown great potential in enhancing the accuracy and efficiency of medical imaging used in infertility diagnosis. In ultrasound imaging, AI algorithms can assist in automating the assessment of ovarian follicles, uterine lining, and other key reproductive structures, allowing for more precise tracking of ovulation and monitoring of reproductive health.[20] Machine learning (ML) models can also analyze subtle changes in imaging data that might be challenging for human eyes to detect, thereby improving diagnostic accuracy and aiding in the early detection of abnormalities such as polycystic ovarian syndrome (PCOS) or endometriosis.[21] Additionally, AI-driven sperm analysis tools have been developed to automatically evaluate sperm count, motility, and morphology, providing a faster and more consistent analysis than manual microscopy, which is highly prone to variability.[22] AI-driven predictive analytics are revolutionizing the ability to assess fertility outcomes and guide personalized treatment plans. Predictive models trained on extensive data, including age, hormonal levels, previous treatment history, and lifestyle factors, can estimate the likelihood of conception through natural means or assisted reproductive techniques like in vitro fertilization (IVF).[23] Such models can also help in predicting the success rates of embryo implantation based on embryo quality and uterine receptivity, allowing for tailored recommendations that optimize the chances of pregnancy.[24] For instance, AI algorithms have been successfully applied to develop embryo selection systems that rank embryos based on quality and implantation potential, helping reduce the time and cost associated with multiple IVF cycles.[25] AI has also expanded its applications into the field of genetic testing and screening, a crucial area in understanding the underlying causes of infertility. By leveraging large datasets of genetic information, machine learning models can identify genetic markers associated with conditions like male infertility, recurrent pregnancy loss, and an increased risk of congenital anomalies.[26] This capability is particularly beneficial for pre-implantation genetic testing, where AI algorithms can evaluate embryos for genetic abnormalities before implantation, thereby improving success rates and reducing the likelihood of genetic disorders in offspring.[27] In genetic counseling, AI can analyze family medical histories and genomic data to provide personalized risk assessments and better inform patients of their reproductive health options.[28]
AI in Fertility Treatment Personalization
Artificial intelligence is transforming in vitro fertilization by improving embryo selection, optimizing ovarian stimulation protocols, and predicting IVF success rates. AI algorithms analyze high-resolution images of embryos, evaluating characteristics that indicate embryo quality and viability, such as cell division patterns and morphokinetics. By identifying embryos with the highest potential for successful implantation, AI-driven systems can help reduce the number of IVF cycles required, leading to lower costs and a less emotionally taxing experience for patients.[29] Furthermore, AI models are also applied to ovarian stimulation protocols, helping to adjust the timing and dosage of hormone injections, improving ovarian response and egg retrieval outcomes.[30]
Fig. no. 1 AI-Driven Personalization in Fertility Treatment
Machine learning (ML) algorithms are highly effective in creating personalized fertility treatment plans by analyzing extensive patient data, including age, hormonal levels, lifestyle factors, and medical history. Through pattern recognition and data correlation, ML can identify specific patient characteristics that influence treatment success, thus enabling fertility specialists to tailor interventions. For example, AI can assess patient profiles to predict whether conventional treatments like intrauterine insemination (IUI) or IVF would be more effective, reducing unnecessary procedures and optimizing outcomes.[31] This data-driven approach not only improves treatment efficacy but also enhances the likelihood of conception by recommending interventions best suited to each individual. AI-driven tools are proving essential in tailoring hormone therapy for infertility, particularly in optimizing doses for ovarian stimulation and managing side effects. Personalized dosing algorithms analyze patient-specific factors such as hormonal responses, body mass index, and reproductive health history to adjust medication plans in real-time, minimizing adverse reactions and maximizing treatment efficacy.[32] For example, AI can help reduce the risks of ovarian hyperstimulation syndrome (OHSS), a common side effect of hormone therapy, by predicting patients who may be at risk and adjusting doses accordingly.[33] These customized approaches in hormone therapy not only enhance treatment safety but also improve the success rates of fertility interventions by providing a precise dosage that aligns with each patient’s unique physiology.
AI and Assisted Reproductive Technologies [ART]
Artificial intelligence has become a critical tool in enhancing the selection of viable embryos during in vitro fertilization. AI algorithms analyze high-resolution time-lapse images of developing embryos, assessing their morphological characteristics and growth patterns. These algorithms can identify subtle features such as cell symmetry, division rates, and blastocyst formation, which are correlated with higher implantation potential and better outcomes. By automating this process, AI helps embryologists select embryos with the highest likelihood of success, reducing subjective bias and human error in embryo assessment. Studies have shown that AI-assisted embryo selection improves the success rates of IVF by optimizing the quality of the embryos selected for implantation.[34,29] The implementation of AI in embryo selection leads to a more objective, data-driven approach to IVF, improving both clinical outcomes and patient satisfaction. AI-driven analysis is also making significant strides in sperm selection, a crucial aspect of IVF and intrauterine insemination. Traditionally, sperm selection was done manually through semen analysis, which is prone to inconsistencies and subjectivity. AI algorithms, however, can evaluate sperm morphology, motility, and viability with high precision, enabling the identification of the healthiest sperm cells. Machine learning models can process large amounts of data to predict which sperm are most likely to result in successful fertilization and embryo development, thereby improving fertilization rates and reducing the risk of genetic abnormalities [35,36]. For instance, AI can help identify sperm with optimal motility and DNA integrity, ensuring that the best sperm are selected for fertilization, which is particularly beneficial in cases of male infertility or low sperm count.
Emerging trends in automated laboratories are paving the way for AI to manage multiple steps in the fertility treatment process, from initial assessment to embryo transfer. In these automated labs, AI systems control tasks such as sperm washing, embryo culture monitoring, and cryopreservation. By reducing human intervention, AI minimizes the risk of error during crucial steps in assisted reproductive technology procedures, such as the risk of cross- contamination, inconsistent environment conditions, or improper embryo handling.[37] AI- based automation allows for real-time monitoring of laboratory conditions, such as temperature and humidity, ensuring optimal conditions for embryo development. Additionally, AI can support the integration of various laboratory instruments and systems, streamlining workflow and improving efficiency. As automation in ART continues to evolve, AI-driven laboratories will become more common, promising to enhance the precision, efficiency, and consistency of fertility treatments.
Fig. 2 Potential AI Targets in Assisted Reproductive Technology (ART)
Artificial intelligence (AI) and machine learning (ML) present various applications across clinical and embryological stages in ART. This excludes infertility investigations and pre- treatment counseling, which are addressed separately in the "Pre-treatment Counseling" section. The specific steps and timing can vary based on the chosen ART protocol. Figure created by the authors.
6. Future Directions and Challenges
As artificial intelligence continues to advance in the field of reproductive medicine, it raises important ethical concerns that need to be addressed. One key issue is privacy, as AI relies heavily on personal data, such as medical histories, genetic information, and sensitive reproductive health data. Protecting this data from breaches and ensuring patients' consent is properly obtained for its use in AI models is paramount. Additionally, AI algorithms could inadvertently reinforce existing biases if the data used to train them is not representative of diverse populations, leading to unequal access to care and potential disparities in treatment outcomes. For example, AI-driven embryo selection or sperm analysis might show varied efficacy depending on genetic backgrounds, socioeconomic status, and geographical location. Another ethical challenge revolves around the moral considerations of AI-driven reproductive choices, such as when to select embryos with certain genetic traits or how to handle genetic abnormalities. The use of AI in decision-making processes regarding embryo selection, sperm choice, and treatment plans could challenge traditional concepts of reproductive autonomy, potentially leading to debates on the regulation and governance of such technologies[38,39]
Potential for Integrative AI Solutions
Looking forward, AI's potential in fertility treatment extends beyond individual interventions and into broader integrative solutions. One promising direction is the integration of AI with telemedicine platforms, enabling remote consultations and continuous monitoring of reproductive health. AI-powered apps and platforms can provide real-time analysis of fertility- related biomarkers, such as hormone levels, ovulation cycles, and sperm quality, to support personalized, data-driven interventions outside of traditional clinic settings. Furthermore, wearable health technologies that track vital signs and environmental factors can be coupled with AI to monitor reproductive health on a continuous basis, giving women and couples a proactive approach to managing fertility. Integrating AI with these technologies can improve early detection of fertility issues, provide ongoing treatment recommendations, and enhance patient engagement through personalized care pathways.[40] This synergy between AI, telemedicine, and wearable tech could revolutionize how fertility care is delivered, making it more accessible and efficient.
Limitations and Risks
While AI holds great promise in transforming fertility medicine, several limitations and risks must be considered. One major challenge is data security. Fertility data, being inherently sensitive, requires robust security measures to prevent hacking or unauthorized access. Given the potential scale of personal data involved in AI-driven fertility treatments, it is crucial to ensure compliance with global privacy regulations, such as GDPR, to safeguard patient confidentiality. Another limitation is the lack of standardization in AI applications across the fertility field. The accuracy of AI models depends heavily on the quality and diversity of data used to train them. Variability in laboratory techniques, equipment, and patient populations can impact the generalizability of AI models across different clinical settings. Moreover, despite the exciting potential of AI, many applications still lack extensive clinical validation and large- scale trials to substantiate their effectiveness. Rigorous, multi-center studies are required to validate AI’s role in fertility treatments, ensuring it is safe, reliable, and effective. These challenges underscore the need for continuous research, careful regulation, and ethical oversight as AI continues to evolve in fertility medicine.[41,42]
CONCLUSION
In conclusion, artificial intelligence has the potential to significantly transform the landscape of infertility management and treatment. From enhancing diagnostic accuracy through imaging and predictive analytics to personalizing fertility treatments and optimizing assisted reproductive technologies, AI offers innovative solutions to longstanding challenges in reproductive medicine. By integrating AI with current fertility practices, clinicians can provide more effective, tailored treatments that maximize the chances of successful conception. Furthermore, AI can help make fertility care more accessible by offering remote consultations, continuous monitoring, and personalized medication adjustments, ultimately improving patient outcomes. Despite its promising potential, the application of AI in infertility treatment requires further research, validation, and ethical oversight. The complexities of data privacy, algorithmic bias, and the need for standardized practices underscore the importance of establishing robust ethical guidelines to ensure the responsible use of AI in reproductive health. Moving forward, interdisciplinary collaboration, including experts in medicine, ethics, and data science, will be essential to harness the full benefits of AI while mitigating potential risks. Continued research and clinical trials will be crucial in refining AI technologies and ensuring their safe, equitable, and effective integration into fertility care, ultimately helping millions of individuals and couples achieve their dream of parenthood.
REFERENCES
Amruta Rajput*, Deokar Shivprasad, Dr. Kawade Rajendra, The Role of Artificial Intelligence in Revolutionizing Infertility Diagnosis and Treatment: Current Applications and Future Directions, Int. J. of Pharm. Sci., 2024, Vol 2, Issue 11, 1413-1422. https://doi.org/10.5281/zenodo.14223718