{"paper_id":"adcd7788-3dde-4921-8724-95cfda01f428","body_text":"Assisted reproductive technology (ART)\nencompasses a broad spectrum\nof medical techniques designed to aid individuals and couples in overcoming\ninfertility challenges, enabling the conception of a child. \n − \n \n \n \n \n \n \n \n  As infertility affects approximately 10–15% of couples worldwide,\nART is a critical component of modern healthcare. \n , \n  Since its start with the birth of the first  in vitro  fertilization (IVF) baby in 1978,  ART\nhas evolved significantly, incorporating groundbreaking scientific\nand technological advancements. These developments have transformed\nthe field of reproductive medicine, offering innovative solutions\nfor diverse reproductive issues and expanding possibilities for parenthood.\nART procedures typically involve the handling of eggs, sperm, and\nembryos to achieve fertilization and implantation. Techniques, such\nas IVF and cryopreservation, are now standard practices in fertility\nclinics worldwide. In recent years, emerging technologies such as\nartificial intelligence (AI), genetic testing, and stem cell research\nhave further refined ART, enhancing its success rates while addressing\nethical and social implications. Furthermore, experimental innovations\nlike  in vitro  gametogenesis (IVG) hold the promise\nof providing gametes for individuals who are unable to produce their\nown, potentially revolutionizing reproductive options for individuals\nwith infertility. Noteworthy, ART is a rapidly advancing field, but\nthe application of certain novel and emerging technologies in humans\nis still highly experimental, tightly regulated, and surrounded by\nvarious ethical and legal challenges. They rely heavily on animal\nmodels, which offer valuable insights into reproductive biology and\nthe effects of various ART interventions. \n −\nAlong\nwith advances and recent success in ART, certain major challenges\nand concerns exist. These include scientific hurdles such as efficiently\nreplicating the complex microenvironment of the gonads in vitro; ensuring\nthe genetic and epigenetic stability of laboratory-generated gametes;\nand achieving successful fertilization, implantation, and development\nusing IVG-derived gametes, to mention a few. Important ethical considerations\ninvolve: (i) safetyrisks of creating embryos from lab-generated\ngametes are unknown; (ii) designer babiespotential misuse\nfor nontherapeutic genetic modifications; (iii) embryo overproductiongenerating\nsurplus embryos raises ethical concerns about their fate; (iv) consent\nand accessdetermining ownership and rights over iPSC-derived\ngametes. Furthermore, regulatory and social acceptance present additional\nchallenges related to ART, for example, public perceptions and cultural\nattitudes toward creating gametes in the lab could pose serious barriers.\nIn this report, we explore data from the CAS Content Collection,  the largest human-curated repository of scientific\ninformation, to outline the research progress in ART. We analyze the\npublication landscape to offer perspective into the latest advancements,\nto identify key emerging concepts and challenges associated with ART.\nWe review the most discussed and emerging concepts and assess the\nstrategies to improve ART. We first explore the traditional methods\nused in ART, with their advantages and shortcomings, then review the\nrecent advancements providing novel options and improving success\nrates. The major types of substance classes commonly associated with\nART have been characterized. The insights from the CAS Content Collection\nallowed us to identify  in vitro  fertilization and\nembryo transfer as the best and most widely explored areas in the\nfield. Furthermore, the fastest growing promising novel methods in\nART have been identified as artificial intelligence integration and  in vitro  gametogenesis. Special attention has been devoted\nto the ethical considerations associated with ART. By exploring its\nscientific basis, clinical applications, and societal impact, the\nreport aims to provide a comprehensive understanding of how ART continues\nto shape the future of reproductive healthcare. The merit of the article\nstems from the extensive, wide-ranging coverage of the most up-to-date\nscientific information, allowing extensive breadth of landscape analysis\nand in-depth insights.\n\nOur search in the\nCAS Content Collection  for ART-related\ndocuments retrieved over 50,000 scientific publications\n(mostly journal articles and patents) for the period 2000–2024.\nThe number of related documents has consistently grown over the last\ntwo decades, more than tripling in that time ( Figure  \n A). Reflecting the early success of  in vitro  fertilization, form the 1980 the number of ART-related\nresearch has exhibited exponential growth ( Figure  \n A, inset).  Figure  \n B summarizes the top patent offices with\nthe most ART-associated patents. The World Intellectual Property Organization\n(WIPO) and the China patent office are notable leaders.\n(A) Number\nof documents (journal articles and patents) related\nto ART in the CAS Content Collection for years 2000–2024. Inset:\nDocument yearly growth from year 1980, with an exponential growth\ntrendline. (B) Top patent offices with patents related to ART. (C)\nDistribution of substances associated with ART in journal (outer donut\nchart) and patent (inner pie chart) publications, broken down by substance\nclass. Data from the CAS Content Collection for the period 2000–2024.\nWe surveyed the substance data extracted from the\nCAS REGISTRY  regarding the types of substance\nclasses commonly\nassociated with ART. Our analysis indicates that proteins/peptides/nucleic\nacids and small molecules are most commonly associated with ART ( Figure  \n C). In patents, proteins/peptides/nucleic\nacids represent ∼60%, and in journals, ∼86% of publications.\nSmall molecules are the second largest group, with 12% in journals\nand ∼40% in patents ( Figure  \n C).\nIndeed, proteins, peptides, and nucleic acids\nplay crucial roles\nin advancing ART. Their applications are expanding with the development\nof emerging biotechnological innovations. Exemplary specific roles\nof proteins, peptides, and nucleic acids in the emerging ART are described\nbelow:\n(i) Growth factors and cytokines: proteins\nlike bone morphogenetic proteins (BMP), insulin-like growth factor\n(IGF), and epidermal growth factor (EGF) improve oocyte maturation,\nsperm motility, and embryo development in culture media; \n , \n  antiapoptotic proteins (e.g., BCL-2) enhance embryo survival. \n , \n  (ii) Hormones and receptors: follicle-stimulating hormone (FSH),\nluteinizing hormone (LH), and hCG are used for ovarian stimulation\nin IVF; \n , \n  zona pellucida proteins (ZP1–4) are\ncritical for sperm-egg binding and fertilization; \n , \n  albumin and serum proteins are used in culture media to stabilize\nembryos and prevent oxidative stress. \n −\n(i) Synthetic peptides for sperm activation:\nCatSper channel-activating peptides can enhance sperm motility for\nICSI.  (ii) Antimicrobial peptides (AMPs)\nare used to prevent bacterial contamination in semen extenders and\nembryo culture media. \n , \n  (iii) Cell-penetrating peptides\n(CPPs) deliver gene-editing tools (CRISPR-Cas9) or protective molecules\n(e.g., antioxidants) into gametes/embryos. \n ,\nDNA/RNA analysis for genetic screening:\n(i) Preimplantation genetic testing (PGT-A/PGT-M) using PCR and NGS\nto screen embryos for aneuploidy or genetic disorders. Sperm RNA profiling\nhelps identify male infertility biomarkers. (ii) Gene editing (CRISPR-Cas9)\ncorrects mutations in embryos (e.g., mitochondrial DNA diseases);\npotential use in synthetic embryos or gametes from stem cells. (iii)\nNoncoding RNAs (miRNAs, lncRNAs): miRNAs regulate oocyte maturation\nand embryo implantation; exosomal RNAs in seminal fluid influence\nembryo development. \n −\n(i) Synthetic proteins/peptides: Custom-designed\nmolecules to improve gamete quality and embryo viability. (ii) Nucleic\nacid therapeutics: mRNA-based treatments to enhance endometrial receptivity.\n(iii) Exosome-based therapies: using extracellular vesicles carrying\nproteins/nucleic acids to improve reproductive outcomes. Proteins,\npeptides, and nucleic acids are revolutionizing ART by enhancing the\nfertilization efficiency, embryo quality, and genetic safety. Future\nadvances may include personalized reproductive medicine using these\nbiomolecules.\nSmall molecules are the second largest\ngroup of substances represented in the ART-related documents, with\n12% in journals and ∼40% in patents. They play several critical\nroles in the emerging trends of ART, enhancing efficiency, safety,\nand success rates. Small molecules (typically <900 Da) are revolutionizing\nART by improving gamete quality, embryo viability, and implantation\nsuccess while enabling cutting-edge techniques like IVG, stem cell-based\nreproduction, and personalized fertility treatments. \n − \n \n \n \n  Their role will expand further with advances in precision reproductive\nmedicine.  Table  \n  summarizes\nthe roles of small molecules in emerging ART.\nThus, key trends enabled by small molecules include:\n(i) precision\nfertilitytargeted modulation of gamete/embryo quality; (ii)\nstem cell-based reproductionlab-generated gametes (IVG); (iii)\nreduced hormonal dependencesafer stimulation protocols; (iv)\nepigenetic safetymitigating ART-induced epigenetic risks;\n(v) cryopreservation advanceshigher post-thaw survival rates.\nPolymers, represented by ∼1% in both\npatents and journal articles related to the field, also play roles\nin ART by improving biocompatibility, structural support, drug delivery,\nand cryopreservation. Their versatility enables advances in embryo\nculture, gamete storage, bioengineered reproductive tissues, and minimally\ninvasive procedures. \n − \n \n  For example, polymers like hyaluronic acid and PEG\nimprove biocompatibility by reducing immune rejection; alginates and\ncollagen provide mechanical support by mimicking ECM for 3D culture;\nPLGA and chitosan nanoparticles provide controlled release for slow\nhormone/drug delivery; PVA and trehalose polymers play a role in cryoprotection,\npreventing freeze damage; fibrin and poloxamer gels play a role in\nbioadhesion, improving embryo transfer success,\n\nEfforts to overcome infertility have a long history, from the first\ndocumented case of artificial insemination in 1790 by John Hunter\nin England,  through the discovery of\nthe hormonal control of ovulation that laid the groundwork for ovarian\nstimulation in ART,  and the introduction\nof cryopreservation techniques for sperm  in the 1950s, further with the development of  in vitro  techniques to study fertilization in mammals, \n , \n  as well as the research on ovarian stimulation and egg retrieval  in the 1960s. The first pregnancy achieved through  in vitro  human fertilization of a human oocyte was reported\nin 1973 although it ended in miscarriage.  It was not until 1978 that the first successful IVF pregnancy and\nlive birth occurred, \n , \n  with the IVF becoming mainstream\nin the 1980s. \n ,\nCurrently, the traditional\nmethods of ART involve established and\nwidely used techniques that have formed the foundation of infertility\ntreatments ( Figure  \n ). These methods primarily focus on the manipulation of eggs, sperm,\nand embryos to enhance the chances of conception.\nTraditional ART methods\n(inner blue-green circle) and recent advancements\n(outer yellow-orange circle).\nIn vitro  fertilization (IVF) is the most well-known ART\nprocedure. It involves a process of fertilization, in which an egg\nis combined with sperm  in vitro . IVF includes the\nsteps of ovarian stimulation using fertility drugs to produce multiple\neggs, retrieval of mature eggs through a minor surgical procedure,\nfertilization of eggs with sperm in a laboratory dish, and transfer\nof resulting embryos into the uterus. Currently fully integrated into\nclinical practice, it is successfully applied in tubal factor infertility,\nendometriosis, male factor infertility, and unexplained infertility.\nIVF is now a cornerstone of human fertility treatment, enabling millions\nof births worldwide. Success rates vary by age, with the highest success\nrates (30–40% per cycle) for women under 35. Rates decline\nsignificantly after age 40. \n −\nArtificial insemination is\na medical procedure in which sperm is introduced into a woman’s\nreproductive tract to facilitate fertilization and pregnancy. A sperm\nsample is collected, washed, and concentrated to isolate healthy sperm\nand then placed directly into the uterus (intrauterine insemination,\nIUI) or cervix (intracervical insemination, ICI) during ovulation.\nIt is mainly applied in cases of mild male infertility, unexplained\ninfertility, and cervical mucus issues. It is simpler and less invasive\nthan IVF. Success rates are typically 10–20% per cycle, depending\non factors like age and sperm quality. \n ,\nGamete intrafallopian\ntransfer (GIFT) is a procedure that helps women conceive by placing\neggs and sperm directly into the fallopian tubes. Eggs and sperm are\ncollected and mixed before being placed into the fallopian tube via\nlaparoscopy, allowing fertilization to occur naturally in the body.\nUsed when one fallopian tube is functioning and there are no significant\nsperm issues. Requires a surgical procedure and general anesthesia.\nIn contrast to IVF, which places fertilized eggs directly into the\nuterus, the GIFT technique allowed the eggs to fertilize and develop\nin the fallopian tube and then find their way to the uterus for implantation.\nIt is less commonly used today due to advances in IVF. \n −\nZygote intrafallopian\ntransfer (ZIFT) is similar to IVF, but the fertilized egg (zygote)\nis transferred into the fallopian tube instead of into the uterus.\nIt is applied for patients with infertility but healthy fallopian\ntubes. Allows the zygote to develop in the natural environment of\nthe fallopian tube. Combines the benefits of IVF and GIFT, but is\nless common now. \n ,\nCryopreservation\n(fertility preservation) involves freezing and storing reproductive\ncells, such as eggs, sperm, and embryos, for future use. Cryopreservation\nis now a routine procedure for embryos and sperm, and is becoming\nmore common for oocytes. It is applied for fertility preservation,\ne.g., for cancer patients undergoing chemotherapy or radiation, with\nexcess embryos from IVF, or delaying childbearing for personal or\nprofessional reasons. Vitrification (rapid freezing) has significantly\nimproved outcomes compared to slow freezing. Success rates depend\non the age at which eggs or sperm are frozen. Long-term storage costs\ncan be significant. \n −\nEgg donation and sperm\ndonation can help people have children when they are not able to produce\nhealthy eggs or sperm on their own. Eggs or sperm are donated by a\nthird party and used in ART procedures such as IVF or intrauterine\ninsemination to achieve pregnancy. Applied for individuals unable\nto produce viable gametes, such as women with premature ovarian failure\nor poor egg quality or men with no viable sperm. Widely used by older\nwomen, same-sex couples, and single parents. Donors are screened for\nmedical and genetic conditions. Legal and ethical issues around donor\nanonymity and parental rights vary by country. \n ,\nSurrogacy involves a woman carrying and giving\nbirth to a child for another person or couple using their embryos\n(gestational surrogacy) or their own egg (traditional surrogacy).\nWhile in traditional surrogacy the surrogate’s egg is fertilized\nwith sperm (via IUI or IVF), making her the biological mother, in\ngestational surrogacy the surrogate carries an embryo created through\nIVF using the intended parents’ or donors’ eggs and\nsperm, so she has no genetic link to the child. Applied for individuals\nwith uterine issues or medical conditions preventing pregnancy, also\nfor same-sex male couples or single men. Surrogacy laws vary widely\nby country and region. \n ,\nAdvantages of the traditional\nART methods described above include: (i) proven track record including\ndecades of successful use and refinement; (ii) customizationcan\nbe tailored to specific infertility causes; (iii) wide availability,\noffered by most fertility clinics worldwide. Traditional ART methods\nremain the backbone of modern infertility treatment, with ongoing\nadvancements improving success rates and patient experiences. Still,\ntraditional ART methods, while groundbreaking and beneficial for many,\ndo have some shortcomings such as high costs, emotional and physical\nstress, lower success rates with age, risk of multiple births, and\nhealth risks including ovarian hyperstimulation syndrome as well as\ncertain ethical and legal Issues. Recent advancements in ART are actively\naddressing these key shortcomings, directly tackling the cost, emotional\nstrain, and physical demands of traditional methods. While challenges\nremain, innovations like AI, simplified protocols, and gentler procedures\nare making fertility treatments more efficient and patient-centric.\nFor example, automation and AI in IVF laboratories, including AI-driven\nembryo selection (e.g., time-lapse imaging and machine learning) reduces\nfailed cycles by picking the best-quality embryos, cutting repeat\nIVF costs; robotic ICSI improves precision, lowering lab costs over\ntime. Next-generation sequencing (NGS) for PGT is now faster and more\naffordable, reducing the costs of failed implantations due to chromosomal\nabnormalities. PGT-A (preimplantation genetic testing for aneuploidy)\nimproves live birth rates per transfer, reducing the emotional toll\nfrom repeated failures. Endometrial receptivity analysis (ERA) ensures\nthat embryos are transferred at the optimal time. Oral ovulation stimulants\n(e.g., Letrozole, Clomiphene) are replacing some injectables, thus\nreducing physical burden. Also, long-acting FSH analogs (e.g., Corifollitropin\nalfa) require fewer injections.\n\nRecent advancements in ART\nare transforming fertility treatments,\nproviding more options, and improving success rates.\nArtificial Intelligence\n(AI) is increasingly being integrated into ART to enhance efficiency,\nprecision, and outcomes. \n − \n \n \n \n \n \n  It has been successfully utilized in several areas.\nFor  embryo selection , AI algorithms analyze embryo images to assess\ntheir quality and potential for successful implantation. \n , \n  These algorithms use: (i) time-lapse imaging: AI monitors embryo\ndevelopment over time, evaluating factors such as morphology, cell\ndivision patterns, and dynamics; (ii) morphokinetic data: algorithms\npredict the likelihood of an embryo developing into a viable pregnancy\nby identifying subtle features not visible to the human eye. AI also\nhelps improve  sperm selection  by (i) sperm motility analysis,\nidentifying the most motile and morphologically normal sperm; (ii)\nDNA integrity checks, assessing DNA fragmentation levels in sperm\nto select the healthiest candidates. \n ,\nMachine\nlearning models analyze multiple data points to  predict\nthe success rate of IVF , including patient history (age, hormonal\nlevels, lifestyle factors), clinical data (ovarian reserve markers,\nendometrial receptivity), and embryo quality metrics. AI can  optimize ovarian stimulation protocols  by personalizing medication\ndosages based on patient-specific responses, and predicting ovarian\nresponse to stimulation, reducing the risk of ovarian hyperstimulation\nsyndrome (OHSS).\nAI-driven  automation  streamlines processes in ART\nlaboratories, including monitoring and controlling incubator conditions,\nstandardizing embryo grading to minimize human error, and managing\ncryopreservation protocols. \n , \n  AI leverages  large data sets  from clinics and research studies to identify\ntrends and factors influencing ART success and improve treatment protocols\nby recognizing patterns in patient and embryo data.\nAI is playing a transformative role in  reducing\ncosts  in artificial reproduction techniques (ART), addressing\none of the\nbiggest barriers to accessibility. The major way for reducing costs\nis via  AI-driven efficiency : Smarter embryo selection (biggest cost-saver): Time-lapse\nimaging + deep learning (e.g., EmbryoScope, LifeWhisperer \n − \n \n \n ) predicts embryo viability with >90% accuracy, reducing failed\ntransfers.\nCost impact: fewer IVF cycles needed per live birth. Optimized ovarian stimulation: Algorithms (e.g., IVF2.0,\nAlife) personalize drug doses based on patient data (AMH, BMI, age),\nminimizing wasted medications. \n , \n  Cost impact: reduces\nmedication costs. Automated sperm analysis:\nTools like YO Sperm Analyzer\nor MobileHome \n − \n \n  provide instant, accurate sperm motility/morphology\nreadings. Cost impact: cuts lab fees for basic diagnostics.\nSmarter embryo selection (biggest cost-saver): Time-lapse\nimaging + deep learning (e.g., EmbryoScope, LifeWhisperer \n − \n \n \n ) predicts embryo viability with >90% accuracy, reducing failed\ntransfers.\nCost impact: fewer IVF cycles needed per live birth.\nOptimized ovarian stimulation: Algorithms (e.g., IVF2.0,\nAlife) personalize drug doses based on patient data (AMH, BMI, age),\nminimizing wasted medications. \n , \n  Cost impact: reduces\nmedication costs.\nAutomated sperm analysis:\nTools like YO Sperm Analyzer\nor MobileHome \n − \n \n  provide instant, accurate sperm motility/morphology\nreadings. Cost impact: cuts lab fees for basic diagnostics.\nLowering emotional and physical burden  (indirect\ncost\nsavings): (i) AI’s improved embryo/sperm selection reduces\npsychological toll and financial strain from multiple IVF attempts;\n(ii) AI models (e.g., Fairtility’s CHLOE ) predict optimal protocols per patient, avoiding costly\ntrial-and-error approaches.\nWhile not yet universal, AI adoption\nin fertility clinics is making\ntreatments more affordable and efficient. In the near future, AI could\ndemocratize access to ART by slashing costs by 30–50% for many\npatients.\nIVG represents a groundbreaking\nadvancement in the field of ART offering new possibilities for addressing\ninfertility, understanding human reproduction, and exploring genetic\ndisorders. \n − \n \n \n  IVG is an experimental technology that enables the creation of sperm\nor eggs from somatic cells such as skin or blood cells. IVG involves\nthe differentiation of pluripotent stem cells (PSCs), such as embryonic\nstem cells (ESCs) or induced pluripotent stem cells (iPSCs), into\ngametes. This process mimics the natural progression of gametogenesis,\nwhere primordial germ cells develop into mature gametes through intricate\nmolecular and cellular pathways. Researchers have successfully produced\nfunctional gametes in animal models such as mice, leading to healthy\noffspring. In 2024, scientists at Kyoto University created precursors\nto human gametes from induced pluripotent stem cells (iPSCs).\nWhile IVG has been successfully demonstrated\nin animal models, translating these techniques to human systems remains\na work in progress due to the complexity of human gametogenesis and\nimportant ethical concerns. Potential uses of IVG include: providing\ngametes for individuals unable to produce viable eggs or sperm; enabling\nsame-sex couples to have genetically related children; and addressing\ninfertility due to age or medical conditions. IVG can be used to study\nearly embryonic development and genetic diseases in controlled environments.\nThere are ethical concerns regarding embryo creation and manipulationit\nmight lead to ethical dilemmas about creating and discarding large\nnumbers of embryos, etc. \n , \n  Safety and efficacy\nneed extensive validation before clinical application. One of the\nprimary safety concern regarding germline editing is the lack of sufficient\ndata on long-term consequences and potential off-target effects.  There is a growing emphasis on involving the\npublic in discussions about the ethical, legal, and social implications\nof genetic material editing.\nStem cell-based therapies\nhave emerged as a promising avenue in ART, leveraging the regenerative\nand differentiation potential of stem cells to enhance reproductive\noutcomes. It is paving the way for advanced reproductive treatments. \n − \n \n \n \n \n  The application of stem cell-based therapies in ART relies on their\nability to (i) differentiate into reproductive cell typesfor\nexample, inducing embryonic stem cells or induced pluripotent stem\ncells to form oocytes or sperm; (ii) secrete growth factorsstem\ncells release paracrine signals that enhance tissue repair and cellular\nfunction; (iii) integrate into host tissuestransplanted stem\ncells can integrate into reproductive tissues, contributing to structural\nand functional recovery.\nIn the context of ART, stem cells hold\npotential in several key areas:\nAge-related decline in the ovarian\nreserve is a major cause of\ninfertility. Mesenchymal stem cells and bone marrow-derived stem cells\nhave shown promise in  regenerating ovarian tissue , improving\nfolliculogenesis, and restoring hormonal balance. \n ,\nStem cell transplantation has demonstrated potential in  restoring\nspermatogenesis  in individuals with azoospermia or other forms\nof male infertility. Spermatogonial stem cells (SSCs) can be harvested,\ncultured, and reintroduced into the testes to reinitiate sperm production. \n ,\nConditions such as Asherman’s syndrome and thin endometrium\npose significant challenges for successful implantation. \n , \n  Endometrial stem cells (ESCs) and MSCs have been explored to  regenerate and enhance endometrial receptivity . \n ,\nAdvanced research has focused on deriving gametes (eggs and\nsperm)\nfrom pluripotent stem cells.  \n In vitro gametogenesis\n(IVG)  represents a potential breakthrough for individuals with\nnonfunctional or absent gametes, offering a new route to biological\nparenthood.\nVarious stem cell types used in ART  are exemplified In  Table  \n .\nOne of the most significant\ntrends in ART is the integration of advanced genetic screening techniques.\nPreimplantation genetic testing (PGT) has become increasingly sophisticated,\nallowing for the detection of chromosomal abnormalities and single-gene\ndisorders in embryos before implantation. \n , \n \n PGT-A (aneuploidy screening) technique screens for chromosomal\nabnormalities, which are a leading cause of implantation failure and\nmiscarriage. Advances in next-generation sequencing (NGS) have improved\nthe accuracy and efficiency of PGT-A, leading to higher success rates\nin IVF cycles. \n , \n \n PGT-M (monogenic disorder) is used to identify embryos\ncarrying specific genetic mutations, enabling couples with hereditary\nconditions to have healthy offspring. The development of CRISPR-Cas9\nand other gene-editing tools has further enhanced the potential for\ncorrecting genetic defects at the embryonic stage. \n , \n \n PGT-SR (structural rearrangements)\nform of testing is\ndesigned for individuals with chromosomal translocations or inversions,\nhelping to identify embryos with balanced chromosomal structures. \n ,\nPGT-A (aneuploidy screening) technique screens for chromosomal\nabnormalities, which are a leading cause of implantation failure and\nmiscarriage. Advances in next-generation sequencing (NGS) have improved\nthe accuracy and efficiency of PGT-A, leading to higher success rates\nin IVF cycles. \n ,\nPGT-M (monogenic disorder) is used to identify embryos\ncarrying specific genetic mutations, enabling couples with hereditary\nconditions to have healthy offspring. The development of CRISPR-Cas9\nand other gene-editing tools has further enhanced the potential for\ncorrecting genetic defects at the embryonic stage. \n ,\nPGT-SR (structural rearrangements)\nform of testing is\ndesigned for individuals with chromosomal translocations or inversions,\nhelping to identify embryos with balanced chromosomal structures. \n ,\nThese advancements not only improve the likelihood of\na successful pregnancy but also reduce the risk of passing on genetic\ndisorders, offering a more personalized approach to reproductive medicine.\nWith advancements in genetic technologies,\nparticularly gene editing, the landscape of ART is evolving to address\nnot only infertility but also the prevention of genetic diseases.\nGene editing in ART holds the promise of reducing heritable disorders,\nimproving embryo selection, and enhancing reproductive success rates.\nIt allows the precise editing of genes in embryos, eggs, or sperm.\nThe CRISPR-Cas9 system is the most prominent tool in gene editing,  enabling precise modifications in the genome.\nBy targeting specific DNA sequences, CRISPR-Cas9 can add, delete,\nor alter genes, making it a valuable technology in addressing inherited\ngenetic disorders in embryos created via  in vitro  fertilization (IVF). \n ,\nGene editing\ncan correct mutations in embryos associated with hereditary diseases\nsuch as cystic fibrosis, sickle cell anemia, and Huntington’s\ndisease, preventing their transmission to future generations. Another\nline of application of gene editing in ART is for enhancement of embryo\nselectiongenetic screening combined with editing can improve\nembryo quality by selecting embryos with the highest potential for\nsuccessful implantation and development. Gene editing can help also  addressing infertility it may help identify and correct\ngenetic causes of infertility, such as chromosomal abnormalities or\nmutations affecting gamete function.\nThe technique is controversial\ndue to the potential for “designer\nbabies” and unintended consequences. Moreover, editing one\ngene could have unforeseen effects on other genes or biological processes,\npotentially causing harm. Currently gene editing is banned for reproductive\npurposes in many countries.  Research\nis ongoing, but clinical use for reproductive purposes remains highly\nregulated. One of the major safety concern regarding gene editing\nis the lack of sufficient data on long-term consequences and possible\noff-target effects.  Unintended mutations\ncould have serious consequences for individuals and future generations\nmaking it crucial to fully understand the potential long-term effects\nbefore clinical application. \n , \n  Even highly precise\ngene editing tools like CRISPR can sometimes make edits at unintended\nlocations in the genome (“off-target effects”), which\ncould lead to unforeseen health complications. \n , \n  Regulatory agencies are increasingly engaging with the scientific\ncommunity to establish frameworks for the safe and ethical use of\ngene-editing technologies. There is a rising urgency to involve the\npublic in debates regarding the ethical, legal, and social implications\nof gene editing.\nMitochondrial replacement\ntherapy (MRT), also known as mitochondrial donation, is a technique\nthat aims to prevent the transmission of mitochondrial DNA (mtDNA)\ndisorders from mother to child. \n − \n \n \n  This involves replacing defective\nmitochondria in an egg or embryo with healthy mitochondria from a\ndonor, preventing mitochondrial diseases in offspring. Thus, MRT has\nbeen used to create embryos with genetic material from three individuals:\nthe mother, the father, and a mitochondrial donor (so-called “three-parent\nbabies”).  MRT raises ethical\nconcerns related to genetic modification and its long-term effects\non future generations. MRT is particularly beneficial for women with\nmitochondrial disorders who wish to have genetically related children.\nThe technology is currently regulated differently across countries,\nwith some permitting its use under strict guidelines and others banning\nit outright.\nGene editing and\nMRT technologies are compared in  Table  \n .\nPNT, pronuclear transfer; MST, maternal\nspindle transfer; PBT, polar body transfer.\nIntracytoplasmic sperm\ninjection (ICSI) is an ART procedure that involves injecting live\nsperm directly into the cytoplasm of a mature egg using a micromanipulation\ntool. The fertilized egg is then cultured and transferred as in IVF\nIt represents a refinement of IVF and is the most common and successful\ntreatment for male infertility caused by sperm issues, such as low\nsperm count, poor motility, or abnormal morphology, or when previous\nIVF attempts have failed. Success rates are similar to IVF, but ICSI\ncan significantly improve fertilization rates in cases of male infertility.\nThere are many ways\nto improve embryo culture systems in ART. These include new culture\nplatform design creating a better microenvironment for embryos, new\nmedia formulations including antioxidants to reduce oxidative damage\nand improve blastocyst development, and perfusion-based systems using\ndynamic media flow instead of static culture. Advances in time-lapse\nimaging and monitoring, \n , \n  and optimized culture\nmedia  allow continuous monitoring of\nembryo development, enabling better selection for transfer and increasing\nimplantation rates.\nNext-generation sequencing\n(NGS) is a genomic testing technology that is used in ART to screen\nembryos for genetic defects. Preimplantation genetic testing (PGT)\nusing NGS helps to identify genetic abnormalities in embryos. It can\nidentify euploidy, aneuploidy, and chromosomal mosaicism.  Using PGT enhances the likelihood of healthy\npregnancies while minimizing the risk of genetic disorders. \n ,\nCryopreservation techniques\nin ART have improved in several ways, including vitrificationa\nrapid freezing process that prevents ice crystal formation, improving\nsurvival rates of frozen gametes and embryos, coupled with improved\nand optimized cryoprotectants, vapor tanks storing tissue in the vapor\nphase of nitrogen instead of immersing it in liquid nitrogen, offering\nbetter survival rates for frozen eggs, sperm, and embryos, increasing\nART success rates. \n , ,\nTechniques such\nas ovarian tissue cryopreservation and artificial ovary development\nare advancing, benefiting individuals facing fertility-affecting medical\ntreatments. Ovarian rejuvenation technique is used to stimulate the\novaries to produce new eggs, particularly in women with diminished\novarian reserve or premature ovarian failure. It may include injecting\nplatelet-rich plasma (PRP) into the ovaries to stimulate tissue repair\nand egg production or stem cells to regenerate ovarian tissue. The\ntechnique is still experimental, with mixed results in early studies. \n −\n(i) Time-lapse\nimagingcontinuous monitoring of embryos without the need for\nmanual handling improves embryo selection and reduces stress on the\nembryos; (ii) Automated IVF systemsrobotics and automation\nare being integrated into laboratories to improve the efficiency and\nconsistency of processes like fertilization and embryo transfer; (iii)\nNoninvasive genetic testingtechniques to assess the genetic\nhealth of embryos using culture media, rather than invasive biopsy,\nare being developed to minimize risks. \n , ,\nResearch into ectogenesis, or artificial\nwomb technology, aims to support the development of embryos outside\nthe human body. Such technology is providing solutions for individuals\nunable to carry pregnancies due to medical or anatomical reasons,\nand advancing neonatal care by supporting extremely premature infants. \n ,\n\nWe\nexamined the assortment of ART-associated concepts in the published\ndocuments (journal articles and patents) in the CAS Content Collection\n( Figure  \n ).\nKey concepts\nrelated to assisted reproductive technologies in CAS\nContent Collection with respective numbers of documents for the period\n2000–2024.\nTraditional technologies such\nas  in vitro \n fertilization  and  embryo transfer , providing major advantages such as proven\ntrack record, including successful customization, as well as wide\navailability, understandably constitute the largest part of ART-related\ndocuments in CAS Content Collection  ( Figure  \n ).\nFigure  \n  illustrates the\nrecent growth (years 2022–2024) and the patent/journal proportions\nfor some of the major ART-related concepts.\nRelative growth of documents\nassociated with the key concepts related\nto ART in CAS Content Collection over the past 3 years (2022–2024)\n(top panel stacked bars) and relative proportions of journal articles\nand patents (bottom row pie charts).\nAs seen in  Figure  \n , artificial intelligence\nand  in vitro  gametogenesis are the fastest growing\nnovel methods in ART in the last three years (2022–2024).\nAI is being used to enhance embryo selection and optimize culture\nconditions, leading to improved success rates. Machine learning helps\nidentify patterns in embryo development and patient responses, enabling\npersonalized treatment plans. Indeed, notable improvements were observed\nin the accuracy of diagnosing and predicting successful outcomes in\nfertility treatments. AI-driven models provided more precise forecasts\nof the optimal timing for clinical interventions such as egg retrieval\nand embryo transfer, which are critical to the success of ART cycles. \n − \n \n \n , , , ,\nIn vitro  gametogenesis offers several potential\nadvantages, including: enabling reproduction for individuals with\nimpaired fertility due to lack of functional sperm or eggs, allowing\nsame-sex couples to have genetically related offspring, providing\ngreater control over genetic selection through embryo screening, and\npotentially reducing the physical burden on women by eliminating the\nneed for ovarian stimulation during egg retrieval; however, this technology\nis still in early stages and raises ethical concerns regarding genetic\nmanipulation and potential misuse. \n , \n  IVG has shown\npromise in animal models, including creating offspring with biological\ncontributions from same-sex parents. While not yet ready for clinical\nuse, it could revolutionize infertility treatments in the future.\nOther methods exhibiting substantial growth in the last three years\ninclude  mitochondrial replacement  and  stem cells\ntherapies  ( Figure  \n ). The relative number of documents associated with  gene editing  methods also increased ( Figure  \n ).\nAs seen from  Figure  \n , bottom row, gene editing and stem-cell-based therapies are the\nmethods with highest patent fraction (13% and 10%, respectively) of\nall documents, which is indicative for high market interest.\nStem cell-based therapies in ART offer potential advantages like\nimproving ovarian reserve function, stimulating follicle development,\nrepairing damaged reproductive tissues, and potentially generating\nnew germ cells, potentially providing hope for individuals struggling\nwith infertility due to conditions like premature ovarian failure\nor low sperm count by leveraging the unique ability of stem cells\nto proliferate and differentiate into specialized cell types. They\nrepresent a cutting-edge approach to address infertility and enhance\nreproductive health. These therapies leverage the regenerative potential\nof stem cells to create gametes, repair reproductive tissues, and\nimprove ART outcomes. \n ,\nGene therapies in ART\noffer the potential to prevent genetic diseases\nin future generations by allowing for the identification and correction\nof genetic mutations in embryos, potentially leading to healthier\nbabies with a reduced risk of inheriting genetic disorders while also\nproviding more options for couples facing infertility due to genetic\nissues; however, ethical concerns and the need for further research\nremain significant challenges. Although in its early stages, gene\nediting is being explored to address infertility caused by genetic\nmutations. This could also potentially correct genetic issues in embryos\nbefore implantation. \n ,\nCurrently, gene editing\nin humans, particularly germline editing\n(which affects eggs, sperm, or embryos and can be passed on to future\ngenerations), is heavily restricted or banned in many countries due\nto ethical, safety, and societal concerns. Indeed, changes made to\ngermline cells are heritable, meaning that they affect future generations.\nThis raises ethical questions about consent, as future generations\ncannot consent to these modifications. \n , − \n \n  There are fears that gene editing could be used for nontherapeutic\nenhancements (e.g., selecting for intelligence, appearance, or athletic\nability), leading to societal inequality and eugenics-like practices. \n , \n  Also, some groups argue that altering human DNA is “playing\nGod” or interferes with natural processes. There are also safety\nconcerns that current gene-editing technologies, such as CRISPR-Cas9,\nare not 100% precise and can cause unintended mutations, which could\nlead to cancer or other health issues. Editing one gene could have\nunforeseen effects on other genes or biological processes, potentially\ncausing harm. Furthermore, there is no global agreement on how gene\nediting should be regulated, leading to a patchwork of laws and guidelines.\nAccess to gene-editing technologies could exacerbate existing inequalities,\nwith only wealthy individuals or countries benefiting.\nThe ban\non germline editing in humans remains largely in place\nglobally, with most countries prioritizing caution and ethical considerations.\nHowever, the rapid pace of technological advancement and the potential\nfor misuse have highlighted the need for stronger international cooperation\nand oversight. While somatic cell editing continues to advance and\nshow promise for treating diseases, the debate over germline editing\nis far from settled with ongoing discussions about its ethical, social,\nand scientific implications.\n\nIt is worth noting that ART is a rapidly advancing field, but the\napplication of certain novel and emerging technologies in humans is\nstill highly experimental, tightly regulated, and surrounded by ethical\nand legal challenges. We further overview the current status of animal\nmodels related to ART. Certain key assisted reproductive technologies\napplied in animals are summarized in the  Supporting Information .\n\nThe development and optimization of assisted reproductive technologies\nrely heavily on animal models, which offer valuable insights into\nreproductive biology and the effects of various ART interventions.\nAnimal models are indispensable in ART research due to their biological\nand physiological similarities to humans and their role in studying\nspecies-specific reproductive processes. Moreover, animal models provide\na controlled environment to study the mechanisms of reproduction,\ntest new technologies, and assess the safety and efficacy of ART interventions.\nThus, animals enable repeated experiments, ensuring consistent data\ncollection; animal research minimizes direct experimentation on humans\nin the initial stages of ART development; certain animal species closely\nresemble human reproductive physiology, making them ideal for translational\nresearch; and models help optimize ART for wildlife and livestock\nwith unique reproductive traits. Furthermore, animal models allow\nfor iterative refinement of techniques, provide insights into developmental\nbiology and long-term effects, and enable high throughput testing\nof interventions. \n −\nThe development and application of\nART in humans and model animals\nfollow parallel tracks, with most techniques undergoing extensive\ntesting in animals before being adapted for human use.\nCommon\nanimal models in ART research include: (i) rodents (mice\nand rats)due to their short reproductive cycles, ease of genetic\nmanipulation, and low cost; (ii) livestock (cattle, sheep, and goats)contributing\nto both agricultural efficiency and wildlife conservation by adapting\ntechniques for endangered species; (iii) nonhuman primatesthe\nclosest models to humans in reproductive biology; (iv) zebrafisha\nunique model for early embryogenesis due to their external fertilization\nand transparent embryos; and (v) wildlife modelssupporting\nglobal conservation efforts by enhancing genetic diversity and population\nrecovery. Techniques applied to animal models vs humans are compared\nin  Table  \n .\nIVF,  in vitro  fertilization;\nICSI, intracytoplasmic sperm injection; IVG,  in vitro  gametogenesis.\nAnimal models remain indispensable in ART research,\nserving as\na bridge to ensure that human applications are safe and effective.\nCertain key assisted reproductive technologies applied in animals\nare summarized in the  Supporting Information .\n\nAlthough the\napplication of particular ART in humans is still highly\nexperimental, tightly regulated, and surrounded by ethical and legal\nchallenges, certain ART methods are already widely available. While\nestablished techniques, such as  in vitro  fertilization\n(IVF), cryopreservation, egg and sperm donation, and surrogacy are\nwidely used to address infertility and help individuals or couples\nconceive, emerging technologies are expanding the boundaries of what\nis possible. Some examples include: (i) time-lapse imaging –\nadvanced embryo monitoring systems improving the selection of viable\nembryos for transfer; (ii) preimplantation genetic testing screening\nembryos for chromosomal abnormalities or inherited conditions, reducing\nthe risk of miscarriage and genetic disorders; (iii) in vitro maturation\nenables immature eggs to mature outside the body, providing an alternative\nfor patients who cannot undergo traditional stimulation protocols;\n(iv) laser-assisted hatching technique helps embryos implant by softening\nthe protective shell (zona pellucida), which can sometimes hinder\nimplantation in older women or those using frozen embryos; (v) AI\nis enhancing embryo selection, predicting treatment outcomes, and\ncustomizing patient protocols; machine learning models analyze patient\ndata to predict the probability of successful pregnancy, tailoring\ntreatment protocols accordingly. Success rates for ART vary based\non factors such as age, the cause of infertility, and the type of\nprocedure. Advanced techniques like genetic testing and AI are helping\nto improve outcomes. \n −\nA concise summary of ART success rates by technique, age group,\nand indication, based on recent data (CDC/SART/ESHRE 2022–2023\nreports \n − \n \n \n \n \n \n ) is presented in  Table  \n . Success rates are measured by live birth per cycle/transfer.\nCDC, Center for Disease Control\nand Prevention, USA;  SART, Society for\nAssisted Reproductive Technologies, USA;  ESHRE, European Society of Human Reproduction and Embryology;  DOR, Diminished Ovarian Reserve.\nAge impact: Success drops sharply after 35 due to egg\nquality decline (aneuploidy rates: ∼30% at 35, ∼80%\nat 42). ICSI vs IVF: ICSI improves fertilization\nin male infertility\nbut does not boost live births if sperm is normal. PGT-A benefit: Highest in women >35 (reduces miscarriage\nrisk by screening abnormal embryos). FET advantage: Frozen transfers often outperform fresh\n(better hormone synchronization).\nAge impact: Success drops sharply after 35 due to egg\nquality decline (aneuploidy rates: ∼30% at 35, ∼80%\nat 42).\nICSI vs IVF: ICSI improves fertilization\nin male infertility\nbut does not boost live births if sperm is normal.\nPGT-A benefit: Highest in women >35 (reduces miscarriage\nrisk by screening abnormal embryos).\nFET advantage: Frozen transfers often outperform fresh\n(better hormone synchronization).\nStatistical analysis of certain aspects of the emerging\ntrends in ART, synthesizing global data (2018–2023) from registries\n(SART/ESHRE/ICMART), \n , \n  and market reports are presented\nbelow:\nGlobal IVF cycles/year\nhave increased from 1.5 M (2010) to ∼3.2 M (2023) (CAGR: 7.1%);\nSuccess rates increase45% (2023) live birth/cycle (women <\n35) vs 32% (2010) due to PGT-A/IVF-ICSI; cost reduction: AI/automation\ncut lab costs by 18–22% (2020–2023).\nLive birth rates\nhave increased in 2022 vs 2015 by 8% for women < 35, by 6% for\nage of 35–37, by 4% for age of 38–40, and is stable\nat 12.1% for women > 40.\n\nART-related patents in the CAS\nContent Collection grow not only\nin numbers but also in formulation and methodology diversity. Summarized\nin  Table  \n  are notable\nrecent patents related to ART, illustrating their diversity.\n\nWhile ART hold\nimmense promise, they come with certain challenges\nand ethical concerns. \n , \n  Ensuring the health of both\nparents and their offspring is paramount. Therefore, safety and efficacy\nneed extensive validation before clinical application. \n , , , −\nCreation and disposal of embryos: Creating more embryos than needed\nraises concerns about what happens to unused embryos. Some view the\ndisposal of embryos as ethically problematic, particularly in cultures\nor religions that ascribe moral status to embryos. The Vatican’s\nDonum Vitae (1987) and Dignitas Personae (2008) declare embryo destruction\nmorally equivalent to abortion, as life begins at conception. \n , \n  Furthermore, many conservative Protestant and Islamic scholars equate\nembryo disposal with “taking a life”, citing Qur’anic\nversus (e.g., Surah Al-An’am 6:151) and biblical texts (e.g.,\nJeremiah 1:5).  Moreover, certain philosophers\nargue embryos are “persons” with moral rights. \n , \n  “Sanctity of Life” vs “Quality of Life”:\nThe former views embryos as inviolable; the latter prioritizes parental\nautonomy and medical utility.\nOther embryo-related ethics issue include also: (i) Embryo selection:\npreimplantation genetic testing allows the selection of embryos free\nfrom genetic disorders but raises concerns about eugenics and the\npotential for “designer babies”; (ii) Cryopreservation:\nLong-term storage raises questions about legal ownership and ethical\nobligations to unused embryos; (iii) Embryonic research: The use of\nembryos in stem cell research is controversial, with some arguing\nit violates the sanctity of life. \n −\nThere are certain issues related\nto parentage and identity concerns: (i) Third-party involvement: Use\nof donors (egg, sperm) and surrogates introduces legal and emotional\ncomplexities regarding parental rights and the child’s right\nto know their genetic origins; (ii) Posthumous reproduction: Using\ngametes or embryos from deceased individuals raises questions about\nconsent and the welfare of the resulting child; (iii) Legal parenthood:\nSurrogacy and gamete donation complicate legal definitions of parenthood,\nleading to custody disputes; (iv) Donor anonymity vs right to know:\nShould children conceived via donor gametes have access to their biological\nparents? (v) Psychological effects: Children born via ART may experience\nidentity struggles if their biological and social parents differ;\n(vi) Same-sex couples and single parents: Societal biases and legal\nhurdles may affect the access of same-sex couples or single individuals\nto ART. \n , −\nEthical issues related\nto genetic engineering include: (i) Gene editing: Technologies like\nCRISPR used in ART raise concerns about unintended consequences, heritable\nchanges, and societal implications of altering human genetics; (ii)\nArtificial gametes and wombs: The creation of gametes from stem cells\nand the development of artificial wombs challenge traditional views\nof reproduction and may blur ethical boundaries; (iii) Germline editing:\nCRISPR-Cas9 allows heritable genetic modifications, raising fears\nof eugenics and unintended consequences; (iv) Nonmedical enhancements:\nEthical concerns arise if gene editing is used for cosmetic traits\n(e.g., height, intelligence) rather than disease prevention; (v) Regulation\nand oversight: How should society balance scientific progress with\nethical boundaries? \n , −\nThere are serious\nethical issues related to commercialization and exploitation of ART:\n(i) Commodification of reproduction: ART commercialization may lead\nto exploitation, particularly of egg donors and surrogates, in countries\nwith less regulatory oversight; (ii) Gender and economic inequalities:\nART can reinforce inequalities, as wealthier individuals have greater\naccess to advanced treatments; (iii) Population dynamics: Widespread\nuse of ART could influence societal norms regarding family size, age\nof parenting, and population demographics; (iv) Egg and sperm donation:\nFinancial incentives may exploit economically vulnerable donors; (v)\nBaby markets: Critics argue that commercializing reproduction commodifies\nhuman life; (vi) Global surrogacy industry: Unregulated markets in\ndeveloping countries raise concerns about coercion and unfair compensation. \n −\nLegal and regulatory issues\nare another aspect of ethics-related problems in ART: (i) Lack of\nstandardized regulations: ART practices and laws vary widely across\ncountries, leading to ethical inconsistencies; (ii) Cross-border reproductive\ncare (reproductive tourism): People traveling to countries with more\nlenient ART laws may exploit loopholes, complicating ethical oversight\nand enforcement; (iii) Privacy and data security: Use of AI and genetic\ndata in ART raises concerns about patient confidentiality and potential\nmisuse of sensitive information. \n , ,\nSpecific ethical issues related to the emerging new trends in ART\nare summarized in  Table  \n .\nThe World Health Organization (WHO) has called for\na global registry\nof human gene-editing research and stricter oversight. \n , \n  The UNESCO International Bioethics Committee has recommended a moratorium\non germline editing. \n − \n \n  In the United States, germline editing is\nnot explicitly banned but is heavily restricted. Federal funds cannot\nbe used for germline editing research, and the FDA is prohibited from\napproving clinical trials involving heritable genetic modifications. \n , \n  Many European countries have laws prohibiting germline editing.\nThe Oviedo Convention explicitly bans heritable genome editing. \n , \n  In China, after the controversial case of He Jiankui (who created\nthe first gene-edited babies in 2018), China introduced stricter regulations\nand penalties for unauthorized gene-editing experiments. \n − \n \n  The UK allows gene editing in embryos for research purposes but\nprohibits implantation of edited embryos.  In 2023, the UK approved CRISPR-based therapies for treating blood\ndisorders like sickle cell anemia and beta-thalassemia, marking a\nsignificant step forward for somatic gene editing.  The International Summit on Human Genome Editing continues\nto debate the ethical and scientific implications of germline editing,\nwith many experts calling for a cautious approach. Australia maintains\na ban on germline editing, with strict penalties for violations.  However, in 2023, the Australian government\nbegan reviewing its gene-editing laws to potentially allow somatic\ncell editing for therapeutic purposes.\n\nART is rapidly evolving with research focused\non improving safety,\nsuccess rates, and accessibility. Future trends involve: (i) tailoring\ntreatments to individual genetic profiles through personalized medicine\napproach; (ii) improving embryo selection and predicting outcomes\nvia AI integration and automation; (iii) expanded accessibility by\ndeveloping lower-cost methods to reach underserved populations; as\nwell as (iv) exploring the long-term health of ART-conceived children\nand refining techniques like artificial gametes.\nEmerging technologies\nin ART are pushing the boundaries of reproductive\nmedicine, offering hope to individuals facing infertility while raising\nprofound ethical and societal questions. From AI-driven embryo selection\nto  in vitro  gametogenesis and gene editing, these\nadvancements promise to redefine parenthood. However, translating\nthese innovations into clinical practice requires careful consideration\nof safety, accessibility, and ethical implications to ensure equitable\nand responsible use. Once an ART innovation proves successful in animal\nmodels, it progresses to clinical trials in humans, beginning with\nsmall, carefully monitored studies. Innovations such as time-lapse\nimaging, laser-assisted hatching, and AI-driven embryo selection have\nall transitioned from theory or animal-based research to human use\nafter rigorous validation.","source_license":"CC-BY-4.0","license_restricted":false}