Innovations and challenges in modern infertility treatment: bridging technology and psychosocial care

Infertility affects 10–15% of couples globally, presenting complex medical and psychosocial challenges. Assisted reproductive technologies (ART), including in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and pre‑ implantation genetic testing (PGT), have revolutionized treatment for conditions like oligospermia, tubal factor infertility, and diminished ovarian reserve. Emerging innovations—such as AI‑ driven embryo selection, micro‑TESE for azoospermia, and in vitro activation (IVA) of follicles—are transforming outcomes for refractory cases. Concur ‑ rently, advancements in vitrification and research on the uterine microbiome offer new diagnostic and therapeutic avenues. Despite these strides, infertility’s emotional toll—marked by anxiety, depression, and stigma—often exac‑ erbates physical challenges and may impair treatment success. This review underscores the imperative to integrate ART with psychosocial support systems, including cognitive‑behavioral therapy (CBT), mindfulness interventions, and patient‑centered counseling. As cutting‑edge technologies like CRISPR gene editing and stem cell therapies advance, ethical considerations and equitable access remain critical. The future of infertility management lies in har‑ monizing technological precision with holistic care to optimize both clinical outcomes and quality of life.

Assisted reproductive technologies (ART), IVF, ICSI, Preimplantation genetic testing, Male infertility, Female infertility, Psychosocial support, CRISPR, Stem cell therapy, Fertility preservation

Infertility, defined as the inability to conceive after 12  months of unprotected intercourse, affects 10–15% of couples worldwide [1 ]. As infertility is not solely a medical issue but also one that deeply impacts emo - tional well-being, psychological distress, and social interactions, addressing these factors is crucial to providing comprehensive care [2 ]. Infertility can trig - ger a complex range of emotions, from sadness and frustration to feelings of guilt and inadequacy [3 ]. The emotional distress experienced by couples is often compounded by societal pressures, stigmatization, and the persistent uncertainty surrounding their fertility journey [4 ]. These emotional and psychological impacts frequently disrupt relationships, challenging both indi - vidual and couple dynamics [5 ]. For many, infertility †Ansar Hussain and Musavir Abbas contributed equally to this work. *Correspondence: Mushtaq Hussain Lashari [email protected] 1 Chongqing Precision Medical Industry Technology Research Institute, Chongqing 400000, China 2 Anhui Province Biomedical Sciences and Health Laboratory, First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China 3 Division of Reproduction and Genetics, University of Science and Technology of China, Hefei 230027, China 4 Department of Zoology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan Page 2 of 15Hussain et al. Middle East Fertility Society Journal (2025) 30:44 treatments can feel isolating and overwhelming, fur - ther emphasizing the need for a holistic approach to care that incorporates both medical interventions and psychosocial support [6 ]. Advances in assisted repro - ductive technologies (ART), including in  vitro fertili - zation (IVF), have dramatically improved success rates over the past few decades [7 ]. As ART has evolved, new techniques such as genetic screening and embryo freez - ing have emerged, offering patients more options and increasing the likelihood of successful outcomes [8 ]. However, despite these technological advancements, ART remains a process fraught with emotional and psy - chological challenges. Patients often undergo multiple treatment cycles, facing the repeated cycle of hope and disappointment, which can lead to heightened stress, anxiety, and emotional strain [9 ]. These advancements, particularly in genetic screen - ing, allow for the identification of chromosomal abnor - malities before embryo implantation, thus increasing the likelihood of successful pregnancies and reducing the incidence of miscarriage [10]. Furthermore, embryo freezing and fertility preservation techniques offer greater flexibility for patients who wish to delay preg - nancy, whether due to medical reasons or personal cir - cumstances [11]. Although these developments provide hope for many, it is essential to acknowledge that ART does not only involve the medical procedures themselves. As ART progresses, it is equally crucial to recognize and address the significant psychological and emotional needs of patients. Psychological distress, including depression and anxiety, is common among individu - als undergoing fertility treatments, and it is essential to integrate mental health care with medical interventions to ensure optimal patient outcomes [12]. Addressing the psychosocial challenges faced by infertility patients can help mitigate emotional distress, improve coping strate - gies, and ultimately enhance both emotional and clinical outcomes [13]. The importance of psychological support cannot be overstated, as it directly impacts the overall well-being of individuals undergoing fertility treatments. In addition to the advancements in ART, fertility pres - ervation has emerged as a key area of focus, especially for individuals who face infertility risks due to medical con - ditions or treatments, such as cancer therapies [14]. The ability to preserve fertility through egg or sperm freezing has expanded the reproductive choices for individuals who may not be ready to conceive or who face the threat of infertility due to medical conditions [15]. These tech - nological innovations provide not only hope for future fertility but also peace of mind during what can be a highly uncertain and distressing period. The integration of fertility preservation with ART has opened new ave - nues for patient care, offering individuals the opportunity to have greater control over their reproductive futures [16]. Infertility brings significant psychological and emo - tional challenges, with emotional distress often linked to treatment failure and the uncertainty of ART [17]. Cou - ples may experience feelings of hopelessness, isolation, and depression throughout the process. Addressing men- tal health is crucial, as it directly impacts clinical out - comes. Providing emotional and psychological support alongside ART is essential for a comprehensive, patient- centered approach to infertility care [18]. Ultimately, the holistic integration of ART with emotional and psycho - logical care can greatly improve the overall patient expe - rience [19]. The latest advances in ART are undoubtedly transforming the landscape of fertility treatment, but the emotional journey of infertility remains a constant and often challenging component [20]. By recognizing the importance of mental health care and supporting patients through both the clinical and emotional aspects of treatment, healthcare providers can ensure that cou - ples receive the most comprehensive and compassionate care possible. This review will explore these advance - ments in ART alongside the psychosocial challenges faced by infertility patients, highlighting the critical need for a balanced approach to treatment that addresses both medical and emotional well-being. Male and female infertility treatment with ART/IVF Infertility affects both men and women and can often be addressed through assisted reproductive technology (ART), including in vitro fertilization (IVF) [21]. Male infertility Male infertility is commonly caused by low sperm count (oligospermia), poor sperm motility (asthenozoo - spermia), or abnormal sperm morphology (teratozoo - spermia) (Fig.  1) [22]. Other factors include obstructive azoospermia (blockages preventing sperm release) or genetic disorders (e.g., Y-chromosome microdeletions, CFTR mutations in congenital absence of the vas def - erens) [23]. Additionally, endocrine disruptions (hypo - gonadism, hyperprolactinemia) and lifestyle factors (smoking, oxidative stress) can further impair spermato - genesis [24]. ART/IVF treatments such as intracytoplasmic sperm injection (ICSI) are highly effective for male infertility, enabling fertilization even with severely compromised sperm parameters [25]. For non-obstructive azoo - spermia, advanced techniques like micro-TESE (micro - surgical testicular sperm extraction) can retrieve viable sperm from seminiferous tubules [26]. Sperm DNA frag - mentation testing and magnetic-activated cell sorting (MACS) are now used to select the most genetically Page 3 of 15 Hussain et al. Middle East Fertility Society Journal (2025) 30:44 intact sperm for ICSI, improving embryo quality [27]. In cases of genetic abnormalities, preimplantation genetic testing (PGT) can screen embryos to prevent transmis - sion [28]. Emerging therapies, such as spermatogonial stem cell transplantation and in  vitro spermatogenesis, hold promise for future treatments. With these advance - ments, IVF/ICSI success rates for male-factor infertility now approach 50–60% per cycle in optimal conditions [29]. The medical dimensions of ART—including treatment duration, cycle history, and the physical side effects of protocols—are profound drivers of psychological dis - tress, but their impact is mediated by the quality of psy - chosocial care and patient counselling. The extended duration of treatment and history of previous cycles significantly elevate anxiety, depression, and stress, as each failure introduces uncertainty and decision fatigue about whether to continue [30–32]. Notably, the psycho - logical burden is often most acute at a moderate duration (1–3  years), before patients develop long-term adapta - tion strategies. Furthermore, the complexity of the pro - cess and concerns over iatrogenic effects from hormone injections and procedures are key stressors. This under - scores a critical need for counselling protocols that are explicitly tailored to the treatment stage, helping patients navigate the emotional volatility of specific medical inter- ventions, manage expectations around side effects, and process the grief of failed cycles. The finding that psycho- logical scores did not differ between AI and ART patients highlights that the inherent uncertainty of any fertility treatment is a primary stressor, suggesting counseling should focus on building resilience to outcome uncer - tainty regardless of the technology used [33]. Ultimately, the negative impact of these medical factors is signifi - cantly exacerbated when patients encounter medical staff with poor communication or inadequate coping guid - ance, emphasizing that clinical excellence must integrate both technical and emotional support. Female infertility Female infertility may result from ovulatory disorders (e.g., PCOS, hypothalamic dysfunction), tubal blockages (due to infections or endometriosis), uterine abnormali - ties (fibroids, adhesions), or diminished ovarian reserve linked to advanced maternal age (Fig.  2) [34]. Endocrine imbalances, such as thyroid disorders or premature ovar - ian insufficiency, further contribute to reproductive chal- lenges. For tubal factor infertility, IVF bypasses fallopian tube dysfunction, while ovulation induction with gon - adotropins addresses anovulation [35]. In cases of severe endometriosis, laparoscopic surgery combined with IVF optimizes outcomes. For women with poor ovarian response, protocols like dual stimulation or progestin primed ovarian stimula - tion protocol may enhance follicular recruitment [36]. Egg donation becomes crucial for those with premature ovarian failure or age-related oocyte depletion [37]. Pre - implantation genetic testing (PGT-A/PGT-M) not only Fig. 1 Male infertility disorders and ART interventions. Visual comparison of normal sperm parameters with male infertility disorders: oligospermia, teratozoospermia, asthenozoospermia, and azoospermia. Highlight diagnostic criteria and the need for ART treatments like IVF/ICSI when such conditions impair natural conception Page 4 of 15Hussain et al. Middle East Fertility Society Journal (2025) 30:44 screens for aneuploidies but also identifies single-gene disorders, significantly improving implantation rates [38]. Emerging techniques like in vitro activation (IVA) of dor- mant follicles and mitochondrial replacement therapy offer experimental hope for refractory cases [39]. With personalized protocols, IVF success rates for female infertility now reach 40–50% per cycle in women under 35, though outcomes decline with advancing age [40]. Advancements in infertility treatments In vitro fertilization (IVF) Since the first successful IVF birth in 1978, in vitro ferti - lization has become a foundational treatment for a wide range of infertility issues [41]. IVF involves retrieving eggs and sperm, fertilizing them in a laboratory setting, and transferring one or more resulting embryos into the uterus (Fig.  3). The technique has evolved dramatically over the years with improvements in laboratory condi - tions, embryo culture media, and cryopreservation meth- ods. These advances have increased success rates and allowed for more flexible treatment options, including fertility preservation and donor gametes [42]. IVF is now widely used to address infertility caused by ovulatory dis - orders, tubal damage, endometriosis, male factor infertil - ity, and unexplained cases, offering many individuals and couples a viable pathway to parenthood [43]. Preimplantation genetic testing for aneuploidy (PGT‑A) A key innovation in in vitro fertilization (IVF) is preim - plantation genetic testing for aneuploidy (PGT-A), which improves embryo selection by identifying chromosomal abnormalities before transfer [44]. This process requires biopsying a few cells from an embryo and analyzing its chromosomal makeup through techniques such as next- generation sequencing (Fig.  4). PGT-A is especially ben - eficial for women of advanced maternal age, couples with recurrent miscarriage, or previous failed IVF attempts, as it helps identify embryos with the correct number of chromosomes [45]. Transferring only chromosomally normal embryos improves implantation rates, reduces the risk of miscarriage, and increases the likelihood of a healthy, full-term pregnancy. By enabling more precise embryo selection, PGT-A enhances both the efficiency and the emotional outcome of IVF cycles. Preimplantation genetic testing for aneuploidy (PGT- A) is a strategy used in IVF to select euploid embryos for transfer, aiming to improve outcomes for couples with advanced maternal age, recurrent miscarriage, or implantation failure. However, its clinical benefit is highly debated, as evidence on its ability to improve cumulative live birth rates is conflicting and appears to be influenced by maternal age and ovarian response. Furthermore, technical limitations, such as the inability to detect small chromosomal abnormalities and the potential for Fig. 2 Female infertility disorders and ART interventions. Illustrates common female infertility conditions: fallopian tube blockage, endometriosis, premature ovarian failure, polycystic ovary syndrome (PCOS), uterine fibroids, and cervical cancer. Highlights how these disorders disrupt natural conception and often require ART interventions like IVF for a successful pregnancy Page 5 of 15 Hussain et al. Middle East Fertility Society Journal (2025) 30:44 misclassifying certain ploidy states, present significant challenges to its diagnostic accuracy [46]. Embryo culture and vitrification Recent advancements in embryo culture systems have significantly improved outcomes for both male and female gametes, optimizing the developmental potential of embryos prior to transfer (Fig.  5) [47]. These culture media now better mimic the natural uterine environ - ment, supporting embryo growth from zygote to blasto - cyst stage. For male-factor infertility, specialized media can enhance sperm-derived embryo quality, while for female patients, improved formulations address age- related oocyte deficiencies. The development of vitrification has been equally transformative for both sexes’ reproductive cells [48]. This ultra-rapid freezing technique preserves not only oocytes and embryos but also sperm and testicular tis - sue with minimal cellular damage. The method’s effec - tiveness has expanded fertility preservation options, allowing cancer patients of both genders to safeguard their reproductive potential before undergoing gonado - toxic treatments [49]. For men, testicular tissue cryopreservation offers hope when sperm cannot be obtained via ejaculation, while women benefit from both oocyte and ovarian tissue [50]. These technologies now enable same-sex couples and individuals facing medical challenges to pursue biological parenthood. The combination of opti - mized culture conditions and reliable cryopreservation has elevated IVF success rates globally, while support - ing emerging applications like fertility extension for transgender individuals undergoing hormonal thera - pies [51]. Fig. 3 Scheme illustrating in vitro and in vivo fertilization. Controlled ovarian stimulation (COS) is used to promote follicle growth, maturation, and ovulation. ART adopts either IVF or ICSI for fertilization. Following fertilization, the preimplantation embryo is cultured in incubators, where suboptimal culture conditions such as pH, oxygen, temperature, and osmolality may affect its further development. Finally, the in vitro‑produced embryo is transferred to the uterus at the cleavage or blastocyst stage. On the other hand, in vivo, the female and male gametes interact together, and the sperm fertilizes the oocyte in the infundibulum. Next, the developing embryo moves towards the uterus interacting with the female reproductive system in a physiologic and optimal environment Page 6 of 15Hussain et al. Middle East Fertility Society Journal (2025) 30:44 Looking ahead, research continues to refine these systems, with investigations into personalized culture media tailored to individual patients’ metabolic needs and AI-driven embryo selection algorithms that fur - ther improve implantation rates [52]. These innovations underscore how modern reproductive technologies increasingly serve diverse populations while pushing the boundaries of fertility science. Artificial intelligence (AI) and machine learning in IVF The integration of artificial intelligence (AI) and machine learning [53] into in vitro fertilization (IVF) protocols has Fig. 4 Preimplantation genetic testing. After fertilization via IVF/ICSI, embryos are cultured and undergo cell/embryobiopsy for genetic analysis. This testing identifies chromosomal or genetic abnormalities. Genetically normal embryos are then selected for uterine transfer to improve implantation success Fig. 5 Freezing and vitrification of embryo. This diagram depicts the process of IVF embryo selection and freezing. After embryos are retrieved during IVF treatment, the high‑quality ones are identified through verification. Some embryos may be transferred immediately, while others are preserved through cryopreservation. The frozen embryos are later thawed and used for a delayed transfer, allowing for better timing and improved success rates Page 7 of 15 Hussain et al. Middle East Fertility Society Journal (2025) 30:44 revolutionized multiple aspects of assisted reproductive technology, significantly enhancing precision and success rates [54]. One of the most impactful applications lies in embryo selection, where AI-driven algorithms analyze high-resolution time-lapse microscopy (TLM) images to assess morphological and morphokinetic parameters. These systems evaluate cleavage patterns, blastocyst for - mation kinetics, and cellular symmetry, outperforming traditional manual grading in predicting implantation potential [55]. Beyond embryo assessment, AI has demonstrated remarkable utility in personalizing ovarian stimula - tion protocols. Advanced predictive models process multi-parametric patient data—including age, hormonal profiles, antral follicle count, and genetic markers—to forecast individual response to gonadotropins [56]. Such tools empower clinicians to optimize medication dos - ages, minimizing risks of ovarian hyperstimulation syn - drome (OHSS) while maximizing oocyte yield. Emerging applications extend to sperm selection, where convolutional neural networks (CNNs) identify spermatozoa with optimal DNA integrity and motil - ity patterns, and endometrial receptivity analysis, where deep learning interprets transcriptomic signatures to pinpoint the ideal window for embryo transfer [57]. The convergence of big data analytics and AI is further ena - bling the development of decision-support systems that integrate electronic medical records with real-time labo - ratory metrics to guide clinical judgments [58]. While these technologies promise to reduce subjec - tivity in IVF, challenges persist regarding algorithmic transparency, dataset diversity, and regulatory standardi - zation [59]. Future directions include federated learn - ing approaches to improve model generalizability across ethnic populations and the incorporation of multi-omics data (proteomic, metabolomic) for holistic embryo via - bility assessments [60]. As validation studies proliferate, AI stands poised to transition from an adjunct tool to a cornerstone of precision reproductive medicine [61]. Emerging techniques and future directions The female reproductive microbiome in infertility diagnosis and treatment Recent studies have highlighted that the female repro - ductive tract hosts specialized microbial communities essential for fertility [62]. A healthy vaginal microbiome is dominated by Lactobacillus (70–95%), maintaining a protective acidic environment, while dysbiosis (< 50% Lactobacillus with overgrowth of Gardnerella or Prevo - tella) increases risks of infection and preterm birth [63]. The cervix relies on Lactobacillus (60–80%) for mucosal defense, with pathogenic overgrowth impairing sperm survival. Even the endometrium requires balanced microbiota (optimal 30–60% Lactobacillus) for embryo implantation—dysbiosis here causes chronic inflam - mation and implantation failure [64]. Gut microbiome imbalances additionally disrupt hormonal regulation, exacerbating conditions like PCOS [65]. Throughout the reproductive tract, microbial disturbances contribute to infertility via inflammation, immune dysfunction, and direct interference with reproductive processes, high - lighting the microbiome’s critical role in female fertility (Fig. 6) [66]. Gene editing the future of fertility treatment: CRISPR‑Cas9 Advance CRISPR-Cas9 gene editing has emerged as a ground - breaking strategy for addressing genetic causes of infer - tility, offering precise correction of mutations that impair reproductive function (Fig.  7) [67]. Recent studies high - light its success in restoring fertility in preclinical models by targeting key genes such as SYCP3, which is crucial for meiotic recombination in oocytes, and AURKC , essential for proper sperm head formation [68]. In female infertil - ity, CRISPR has shown potential to rescue FIGLA muta - tions responsible for primordial follicle depletion, while in male infertility cases, it can correct CFTR variants underlying obstructive azoospermia [69]. Research has also demonstrated CRISPR’s ability to reverse epigenetic silencing of LINE-1 retrotransposons in aged oocytes, restoring their developmental competence [70]. While challenges like off-target effects and efficient delivery to gonadal tissues persist, innovations in nanoparticle- based delivery systems and ex vivo gamete editing tech - niques are accelerating clinical translation [71]. This technology not only enhances our understanding of infertility’s genetic basis but also paves the way for per - sonalized therapies, potentially revolutionizing assisted reproductive technologies [71]. Stem cell applications in infertility treatment Although significant progress has been made in ART, many couples are still unable to have healthy biologi - cal children without gamete donation or adoption [72]. Infertility caused by gamete deficiencies due to genetic defects often remains unaffected by ART [73]. Most couples, however, seek treatments that enable the birth of genetically related children through less invasive and more cost-effective methods. In this regard, stem cell therapies offer new hope, as shown in various experimen- tal preclinical and clinical models [74]. Stem cells, found in embryos and adult tissues, have the ability to self-renew and differentiate when needed [75]. In fully developed organs, they help restore func - tion by repairing damage. Stem cells are categorized based on their origin into embryonic stem cells (ESCs), Page 8 of 15Hussain et al. Middle East Fertility Society Journal (2025) 30:44 adult stem cells (including mesenchymal stem cells, MSCs), induced pluripotent stem cells (iPSCs), sper - matogonial stem cells (SSCs), and ovarian stem cells [76]. The process has been illustrated in Fig. 8 . Psychosocial impact of infertility Psychological and emotional distress Infertility can be a deeply distressing experience, with emotional impacts that extend far beyond the clinical Fig. 6 Schematic representation of the female reproductive microbiome and its impact on fertility. A Healthy state: The vaginal, cervical, and endometrial microbiomes are predominantly populated by Lactobacillus species (depicted in blue), which maintain a protective acidic environment and support reproductive health. B Dysbiotic state: A shift in the microbial composition, characterized by a reduction in beneficial Lactobacillus and an overgrowth of pathogenic bacteria such as Gardnerella and Prevotella (depicted in red and orange), creates a pro‑inflammatory environment. This dysbiosis is associated with adverse outcomes including implantation failure, preterm birth, and conditions like PCOS, which can be influenced by gut microbiome imbalances (illustrated on the left) Fig. 7 Embryo gene editing and transfer process. This figure shows the process of embryo gene modification starting with IVF or ICSI. Embryos undergo gene editing through techniques like microinjection or electroporation. After modification and biopsy, selected embryos are allowed to develop and are then transferred to the uterus Page 9 of 15 Hussain et al. Middle East Fertility Society Journal (2025) 30:44 aspects of treatment. Research shows that psychologi - cal distress, including anxiety, depression, and feelings of hopelessness, is common among individuals undergo - ing ART (Fig. 9) [77]. A longitudinal study in 2023 found that almost 50% of women undergoing IVF reported experiencing significant emotional distress, which can negatively affect their mental health and relationship dynamics [78]. Moreover, the emotional toll of infertility can have a detrimental effect on treatment outcomes. Studies sug - gest that stress and emotional distress can lower the chances of successful pregnancies through IVF [79]. Therefore, psychological support is critical in optimizing both emotional well-being and treatment success. Coping mechanisms and social support Many individuals undergoing infertility treatments rely on various coping strategies to manage their emotional distress. Cognitive-behavioral therapy (CBT), mindful - ness meditation, and participation in support groups have been shown to reduce stress and improve psy - chological outcomes for couples [80]. Fertility-specific counseling and therapy can help individuals and couples navigate the emotional journey of infertility, supporting mental health and improving overall treatment satisfac - tion [81]. Support groups, both in-person and online, provide a platform for individuals to share experiences and receive emotional support from others facing similar struggles Fig. 8 Stem cell reprogramming pathway for generating fertile germ cells.This schematic illustrates the stepwise conversion of adult somatic cells (fibroblasts/blood cells) into functional germ cells through an iPSC intermediate. Key stages include (1) somatic cell reprogramming using Yamanaka factors (OCT‑4/KLF4), (2) primordial germ cell induction via cytokine signaling, and (3) differentiation into fertilizable oocyte/ spermatid‑like cells to overcome genetic infertility Page 10 of 15Hussain et al. Middle East Fertility Society Journal (2025) 30:44 [82]. Professional counseling, including couples therapy, has been shown to improve coping mechanisms, reduce relationship strain, and enhance emotional resilience during ART cycles [83]. Social stigma and cultural barriers The global stigma of infertility Infertility carries significant social stigma in many cul - tures, often leading individuals to experience shame, guilt, and isolation due to their inability to conceive [84]. In many societies, parenthood is closely tied to per - sonal identity, marital stability, and social status, mak - ing infertility a highly sensitive issue [85]. This stigma is particularly pronounced in regions such as South Asia, sub-Saharan Africa, and parts of the Middle East, where childbearing is deeply interwoven with cultural and familial expectations [86]. Women, in particular, bear the brunt of infertility stigma, often facing discrimina - tion, exclusion, and even divorce or abandonment due to their inability to conceive [87]. The burden of infertil - ity stigma extends beyond the personal level, influencing healthcare-seeking behaviors, delaying medical interven - tion, and exacerbating emotional distress among affected individuals [88]. The psychological and social consequences of infertility stigma The stigma associated with infertility often results in severe psychological distress, including anxiety, depres - sion, and low self-esteem [89]. Many individuals report feeling a loss of purpose, social alienation, and dimin - ished self-worth due to their inability to fulfill soci - etal and familial expectations of parenthood [90]. In patriarchal societies, women are frequently blamed for infertility, even when male factor infertility is a signifi - cant contributor to childlessness [91]. This blame can lead to emotional and physical abuse, social isolation, and diminished quality of life. The pressure to conceive may also strain relationships, causing marital discord and leading to emotional withdrawal between part - ners [92]. Additionally, the stigma surrounding infer - tility often deters individuals from openly discussing their struggles or seeking medical assistance. Many fear judgment from family, friends, and even healthcare providers, leading to delayed diagnosis and treatment [93]. The lack of open conversations about infertility in certain cultures reinforces misinformation and miscon - ceptions, further marginalizing those affected [94]. Fig. 9 The complex interplay of factors influencing infertility. This figure outlines factors contributing to infertility, categorized into lifestyle, genetic, and psycho‑social‑economic dimensions. It highlights modifiable risks like obesity and smoking, genetic disorders, and the psychological and socio‑economic impacts such as depression and relationship strain. These factors emphasize infertility as a complex interplay of physical, genetic, and emotional elements Page 11 of 15 Hussain et al. Middle East Fertility Society Journal (2025) 30:44 Cultural and religious influences on infertility perceptions Cultural and religious beliefs play a significant role in shaping societal attitudes toward infertility [95]. In many traditional societies, infertility is often viewed as divine punishment, karma, or the result of past sins [96]. Such beliefs can reinforce stigma, discouraging couples from seeking medical interventions such as assisted repro - ductive technologies (ART). In contrast, some religious communities have gradually begun to accept ART, recog- nizing the role of medical science in overcoming infertil - ity while adhering to ethical and moral guidelines [97]. The degree of acceptance, however, varies widely, and in many cultures, ART remains inaccessible or stigmatized due to religious constraints and ethical concerns [98]. Addressing infertility stigma through education and awareness Public education and awareness campaigns are crucial in reducing the stigma surrounding infertility. Provid - ing accurate information about infertility, its causes, and available treatments can help dispel myths and encour - age a more supportive and understanding society [99]. Media, healthcare professionals, and advocacy organiza - tions play a key role in normalizing conversations around infertility and promoting reproductive health education. Involving community and religious leaders in discussions on infertility can also facilitate cultural shifts toward greater acceptance and support for affected individuals [100]. Integrating psychological support in infertility care Healthcare providers must adopt a holistic approach that integrates psychological support into infertility care. Counseling services, peer support groups, and mental health interventions can help individuals cope with the emotional burden of infertility [101]. Cognitive-behav - ioral therapy (CBT), mindfulness techniques, and fer - tility counseling have been shown to reduce stress and improve psychological resilience among patients under - going fertility treatments [6]. Providing accessible and culturally sensitive mental health services can help indi - viduals navigate the emotional challenges of infertility while mitigating the negative effects of societal stigma as the guidelines provided by the ESHERE manual (Fig.  10) [102, 103]. Encouraging policy and institutional support Governments and healthcare institutions have a role to play in reducing infertility stigma by ensuring that repro - ductive health services are accessible, affordable, and inclusive [104]. Policies that promote insurance coverage for fertility treatments, workplace accommodations for individuals undergoing ART, and mental health support in fertility clinics can contribute to a more supportive environment [105]. In addition, legal protections against discrimination based on infertility status can help safe - guard the rights of affected individuals, ensuring that they do not face workplace bias, social exclusion, or une - qual access to healthcare. Fig. 10 Visual guide outlining a stage‑specific psychosocial care protocol for infertility and ART, customized to individual patient requirements Page 12 of 15Hussain et al. Middle East Fertility Society Journal (2025) 30:44

The field of infertility treatment has witnessed remark - able progress through assisted reproductive technolo - gies (ART), yet significant challenges remain. Over recent decades, innovations such as IVF/ICSI, preim - plantation genetic testing, and vitrification techniques have dramatically improved success rates, offering hope to millions of couples worldwide. These technological advancements now enable clinicians to address previ - ously untreatable causes of infertility, from severe male factor infertility to age-related ovarian decline. The integration of artificial intelligence for embryo selec - tion and emerging gene editing technologies promises to further enhance treatment precision and outcomes in the coming years. However, the emotional and psychological burdens associated with infertility continue to pose substan - tial challenges for patients and clinicians alike. Despite technological progress, the infertility journey remains fraught with stress, anxiety, and profound emotional upheaval. Studies consistently show that 30–50% of ART patients experience clinically significant psycho - logical distress [106–108], which may negatively impact treatment adherence and outcomes. The cyclical nature of ART treatment—with its alternating periods of hope and disappointment—creates unique mental health chal - lenges that demand specialized support services and interventions. Moving forward, the field must prioritize three key areas to optimize patient care. First, continued research into personalized treatment approaches through AI and multi-omics technologies will be crucial for improving success rates while minimizing risks. Second, addressing disparities in access to care remains an ethical impera - tive, particularly for costly emerging therapies like stem cell applications and fertility preservation. Finally, and perhaps most importantly, the integration of psychoso - cial support must become standard practice in fertility clinics worldwide. This includes routine mental health screening, counseling services, and support groups to help patients navigate the complex emotional terrain of infertility treatment. Ultimately, the most effective infertility care will har - monize cutting-edge reproductive technologies with comprehensive psychosocial support. By addressing both the biological and emotional dimensions of infer - tility, clinicians can provide truly patient-centered care that optimizes both clinical outcomes and quality of life. As research continues to push the boundaries of repro - ductive medicine, maintaining this balanced, holistic approach will be essential for meeting the diverse needs of individuals and couples facing infertility. The future of infertility treatment lies not just in technological innovation, but in our ability to integrate these advances with compassionate, whole-person care. Abbreviations ART Assisted reproductive technologies IVF In vitro fertilization ICSI Intracytoplasmic sperm injection PGT‑A Preimplantation genetic testing for aneuploidy PGT‑M Preimplantation genetic testing for monogenic disorders CBT Cognitive ‑behavioral therapy AI Artificial intelligence IVA In vitro activation CRISPR Clustered regularly interspaced short palindromic repeats MACS Magnetic‑activated cell sorting TESE Testicular sperm extraction PCOS Polycystic ovary syndrome OHSS Ovarian hyperstimulation syndrome Authors’ contributions A.H., and M.A., have gathered data, outlined and finalized the initial manu‑ script draft. G.M., M.L., Z.U.A., Y.R., A.M., and A.U., helped to analyze data. M.H.L., provided revisions and finalized the manuscript. All authors have reviewed and approved the final manuscript. Funding Not applicable. Data availability The authors confirm that all the data have already been presented in the article. Declarations Ethics approval and consent to participate Not applicable. Consent for publication After reviewing the manuscript, the authors have decided to submit it for publication. The authors declare that nothing in the study has ever been pub‑ lished before or is presently being considered for publication anywhere. Competing interests The authors declare no competing interests. Received: 9 May 2025 Accepted: 18 September 2025

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