{"paper_id":"e61bb767-208a-4b3b-8b86-369c34d69e07","body_text":"Hussain et al. \nMiddle East Fertility Society Journal           (2025) 30:44  \nhttps://doi.org/10.1186/s43043-025-00257-2\nREVIEW Open Access\n© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which \npermits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the \noriginal author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or \nother third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line \nto the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory \nregulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this \nlicence, visit http://creativecommons.org/licenses/by/4.0/.\nMiddle East Fertility\nSociety Journal\nInnovations and challenges in modern \ninfertility treatment: bridging technology \nand psychosocial care\nAnsar Hussain1†, Musavir Abbas2,3†, Zain‑ul‑Abideen2,3, Ghulam Mustafa2,3, Muhammad Lateef2,3, \nAbu Mansoor2,3, Yousaf Raza2,3, Ahmad Hayat4 and Mushtaq Hussain Lashari4* \nAbstract \nInfertility affects 10–15% of couples globally, presenting complex medical and psychosocial challenges. Assisted \nreproductive technologies (ART), including in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and pre‑\nimplantation genetic testing (PGT), have revolutionized treatment for conditions like oligospermia, tubal factor \ninfertility, and diminished ovarian reserve. Emerging innovations—such as AI‑ driven embryo selection, micro‑TESE \nfor azoospermia, and in vitro activation (IVA) of follicles—are transforming outcomes for refractory cases. Concur ‑\nrently, advancements in vitrification and research on the uterine microbiome offer new diagnostic and therapeutic \navenues. Despite these strides, infertility’s emotional toll—marked by anxiety, depression, and stigma—often exac‑\nerbates physical challenges and may impair treatment success. This review underscores the imperative to integrate \nART with psychosocial support systems, including cognitive‑behavioral therapy (CBT), mindfulness interventions, \nand patient‑centered counseling. As cutting‑edge technologies like CRISPR gene editing and stem cell therapies \nadvance, ethical considerations and equitable access remain critical. The future of infertility management lies in har‑\nmonizing technological precision with holistic care to optimize both clinical outcomes and quality of life.\nKeywords Assisted reproductive technologies (ART), IVF, ICSI, Preimplantation genetic testing, Male infertility, Female \ninfertility, Psychosocial support, CRISPR, Stem cell therapy, Fertility preservation\nIntroduction\nInfertility, defined as the inability to conceive after \n12  months of unprotected intercourse, affects 10–15% \nof couples worldwide [1 ]. As infertility is not solely a \nmedical issue but also one that deeply impacts emo -\ntional well-being, psychological distress, and social \ninteractions, addressing these factors is crucial to \nproviding comprehensive care [2 ]. Infertility can trig -\nger a complex range of emotions, from sadness and \nfrustration to feelings of guilt and inadequacy [3 ]. The \nemotional distress experienced by couples is often \ncompounded by societal pressures, stigmatization, and \nthe persistent uncertainty surrounding their fertility \njourney [4 ]. These emotional and psychological impacts \nfrequently disrupt relationships, challenging both indi -\nvidual and couple dynamics [5 ]. For many, infertility \n†Ansar Hussain and Musavir Abbas contributed equally to this work.\n*Correspondence:\nMushtaq Hussain Lashari\nmushtaq.hussain@iub.edu.pk\n1 Chongqing Precision Medical Industry Technology Research Institute, \nChongqing 400000, China\n2 Anhui Province Biomedical Sciences and Health Laboratory, First \nAffiliated Hospital of USTC, Hefei National Laboratory for Physical \nSciences at Microscale, the CAS Key Laboratory of Innate Immunity \nand Chronic Disease, School of Basic Medical Sciences, Division of Life \nSciences and Medicine, University of Science and Technology of China, \nHefei 230027, China\n3 Division of Reproduction and Genetics, University of Science \nand Technology of China, Hefei 230027, China\n4 Department of Zoology, The Islamia University of Bahawalpur, \nBahawalpur 63100, Pakistan\n\nPage 2 of 15Hussain et al. Middle East Fertility Society Journal           (2025) 30:44 \ntreatments can feel isolating and overwhelming, fur -\nther emphasizing the need for a holistic approach to \ncare that incorporates both medical interventions and \npsychosocial support [6 ]. Advances in assisted repro -\nductive technologies (ART), including in  vitro fertili -\nzation (IVF), have dramatically improved success rates \nover the past few decades [7 ]. As ART has evolved, new \ntechniques such as genetic screening and embryo freez -\ning have emerged, offering patients more options and \nincreasing the likelihood of successful outcomes [8 ]. \nHowever, despite these technological advancements, \nART remains a process fraught with emotional and psy -\nchological challenges. Patients often undergo multiple \ntreatment cycles, facing the repeated cycle of hope and \ndisappointment, which can lead to heightened stress, \nanxiety, and emotional strain [9 ].\nThese advancements, particularly in genetic screen -\ning, allow for the identification of chromosomal abnor -\nmalities before embryo implantation, thus increasing \nthe likelihood of successful pregnancies and reducing \nthe incidence of miscarriage [10]. Furthermore, embryo \nfreezing and fertility preservation techniques offer \ngreater flexibility for patients who wish to delay preg -\nnancy, whether due to medical reasons or personal cir -\ncumstances [11]. Although these developments provide \nhope for many, it is essential to acknowledge that ART \ndoes not only involve the medical procedures themselves. \nAs ART progresses, it is equally crucial to recognize \nand address the significant psychological and emotional \nneeds of patients. Psychological distress, including \ndepression and anxiety, is common among individu -\nals undergoing fertility treatments, and it is essential to \nintegrate mental health care with medical interventions \nto ensure optimal patient outcomes [12]. Addressing the \npsychosocial challenges faced by infertility patients can \nhelp mitigate emotional distress, improve coping strate -\ngies, and ultimately enhance both emotional and clinical \noutcomes [13]. The importance of psychological support \ncannot be overstated, as it directly impacts the overall \nwell-being of individuals undergoing fertility treatments.\nIn addition to the advancements in ART, fertility pres -\nervation has emerged as a key area of focus, especially for \nindividuals who face infertility risks due to medical con -\nditions or treatments, such as cancer therapies [14]. The \nability to preserve fertility through egg or sperm freezing \nhas expanded the reproductive choices for individuals \nwho may not be ready to conceive or who face the threat \nof infertility due to medical conditions [15]. These tech -\nnological innovations provide not only hope for future \nfertility but also peace of mind during what can be a \nhighly uncertain and distressing period. The integration \nof fertility preservation with ART has opened new ave -\nnues for patient care, offering individuals the opportunity \nto have greater control over their reproductive futures \n[16].\nInfertility brings significant psychological and emo -\ntional challenges, with emotional distress often linked to \ntreatment failure and the uncertainty of ART [17]. Cou -\nples may experience feelings of hopelessness, isolation, \nand depression throughout the process. Addressing men-\ntal health is crucial, as it directly impacts clinical out -\ncomes. Providing emotional and psychological support \nalongside ART is essential for a comprehensive, patient-\ncentered approach to infertility care [18]. Ultimately, the \nholistic integration of ART with emotional and psycho -\nlogical care can greatly improve the overall patient expe -\nrience [19]. The latest advances in ART are undoubtedly \ntransforming the landscape of fertility treatment, but \nthe emotional journey of infertility remains a constant \nand often challenging component [20]. By recognizing \nthe importance of mental health care and supporting \npatients through both the clinical and emotional aspects \nof treatment, healthcare providers can ensure that cou -\nples receive the most comprehensive and compassionate \ncare possible. This review will explore these advance -\nments in ART alongside the psychosocial challenges \nfaced by infertility patients, highlighting the critical need \nfor a balanced approach to treatment that addresses both \nmedical and emotional well-being.\nMale and female infertility treatment with ART/IVF\nInfertility affects both men and women and can often \nbe addressed through assisted reproductive technology \n(ART), including in vitro fertilization (IVF) [21].\nMale infertility\nMale infertility is commonly caused by low sperm \ncount (oligospermia), poor sperm motility (asthenozoo -\nspermia), or abnormal sperm morphology (teratozoo -\nspermia) (Fig.  1) [22]. Other factors include obstructive \nazoospermia (blockages preventing sperm release) or \ngenetic disorders (e.g., Y-chromosome microdeletions, \nCFTR mutations in congenital absence of the vas def -\nerens) [23]. Additionally, endocrine disruptions (hypo -\ngonadism, hyperprolactinemia) and lifestyle factors \n(smoking, oxidative stress) can further impair spermato -\ngenesis [24].\nART/IVF treatments such as intracytoplasmic sperm \ninjection (ICSI) are highly effective for male infertility, \nenabling fertilization even with severely compromised \nsperm parameters [25]. For non-obstructive azoo -\nspermia, advanced techniques like micro-TESE (micro -\nsurgical testicular sperm extraction) can retrieve viable \nsperm from seminiferous tubules [26]. Sperm DNA frag -\nmentation testing and magnetic-activated cell sorting \n(MACS) are now used to select the most genetically \n\nPage 3 of 15\nHussain et al. Middle East Fertility Society Journal           (2025) 30:44 \n \nintact sperm for ICSI, improving embryo quality [27]. In \ncases of genetic abnormalities, preimplantation genetic \ntesting (PGT) can screen embryos to prevent transmis -\nsion [28]. Emerging therapies, such as spermatogonial \nstem cell transplantation and in  vitro spermatogenesis, \nhold promise for future treatments. With these advance -\nments, IVF/ICSI success rates for male-factor infertility \nnow approach 50–60% per cycle in optimal conditions \n[29].\nThe medical dimensions of ART—including treatment \nduration, cycle history, and the physical side effects of \nprotocols—are profound drivers of psychological dis -\ntress, but their impact is mediated by the quality of psy -\nchosocial care and patient counselling. The extended \nduration of treatment and history of previous cycles \nsignificantly elevate anxiety, depression, and stress, as \neach failure introduces uncertainty and decision fatigue \nabout whether to continue [30–32]. Notably, the psycho -\nlogical burden is often most acute at a moderate duration \n(1–3  years), before patients develop long-term adapta -\ntion strategies. Furthermore, the complexity of the pro -\ncess and concerns over iatrogenic effects from hormone \ninjections and procedures are key stressors. This under -\nscores a critical need for counselling protocols that are \nexplicitly tailored to the treatment stage, helping patients \nnavigate the emotional volatility of specific medical inter-\nventions, manage expectations around side effects, and \nprocess the grief of failed cycles. The finding that psycho-\nlogical scores did not differ between AI and ART patients \nhighlights that the inherent uncertainty of any fertility \ntreatment is a primary stressor, suggesting counseling \nshould focus on building resilience to outcome uncer -\ntainty regardless of the technology used [33]. Ultimately, \nthe negative impact of these medical factors is signifi -\ncantly exacerbated when patients encounter medical staff  \nwith poor communication or inadequate coping guid -\nance, emphasizing that clinical excellence must integrate \nboth technical and emotional support.\nFemale infertility\nFemale infertility may result from ovulatory disorders \n(e.g., PCOS, hypothalamic dysfunction), tubal blockages \n(due to infections or endometriosis), uterine abnormali -\nties (fibroids, adhesions), or diminished ovarian reserve \nlinked to advanced maternal age (Fig.  2) [34]. Endocrine \nimbalances, such as thyroid disorders or premature ovar -\nian insufficiency, further contribute to reproductive chal-\nlenges. For tubal factor infertility, IVF bypasses fallopian \ntube dysfunction, while ovulation induction with gon -\nadotropins addresses anovulation [35]. In cases of severe \nendometriosis, laparoscopic surgery combined with IVF \noptimizes outcomes.\nFor women with poor ovarian response, protocols like \ndual stimulation or progestin primed ovarian stimula -\ntion protocol may enhance follicular recruitment [36]. \nEgg donation becomes crucial for those with premature \novarian failure or age-related oocyte depletion [37]. Pre -\nimplantation genetic testing (PGT-A/PGT-M) not only \nFig. 1 Male infertility disorders and ART interventions. Visual comparison of normal sperm parameters with male infertility disorders: oligospermia, \nteratozoospermia, asthenozoospermia, and azoospermia. Highlight diagnostic criteria and the need for ART treatments like IVF/ICSI when such \nconditions impair natural conception\n\nPage 4 of 15Hussain et al. Middle East Fertility Society Journal           (2025) 30:44 \nscreens for aneuploidies but also identifies single-gene \ndisorders, significantly improving implantation rates [38]. \nEmerging techniques like in vitro activation (IVA) of dor-\nmant follicles and mitochondrial replacement therapy \noffer experimental hope for refractory cases [39]. With \npersonalized protocols, IVF success rates for female \ninfertility now reach 40–50% per cycle in women under \n35, though outcomes decline with advancing age [40].\nAdvancements in infertility treatments\nIn vitro fertilization (IVF)\nSince the first successful IVF birth in 1978, in vitro ferti -\nlization has become a foundational treatment for a wide \nrange of infertility issues [41]. IVF involves retrieving \neggs and sperm, fertilizing them in a laboratory setting, \nand transferring one or more resulting embryos into the \nuterus (Fig.  3). The technique has evolved dramatically \nover the years with improvements in laboratory condi -\ntions, embryo culture media, and cryopreservation meth-\nods. These advances have increased success rates and \nallowed for more flexible treatment options, including \nfertility preservation and donor gametes [42]. IVF is now \nwidely used to address infertility caused by ovulatory dis -\norders, tubal damage, endometriosis, male factor infertil -\nity, and unexplained cases, offering many individuals and \ncouples a viable pathway to parenthood [43].\nPreimplantation genetic testing for aneuploidy (PGT‑A)\nA key innovation in in vitro fertilization (IVF) is preim -\nplantation genetic testing for aneuploidy (PGT-A), which \nimproves embryo selection by identifying chromosomal \nabnormalities before transfer [44]. This process requires \nbiopsying a few cells from an embryo and analyzing its \nchromosomal makeup through techniques such as next-\ngeneration sequencing (Fig.  4). PGT-A is especially ben -\neficial for women of advanced maternal age, couples with \nrecurrent miscarriage, or previous failed IVF attempts, \nas it helps identify embryos with the correct number of \nchromosomes [45]. Transferring only chromosomally \nnormal embryos improves implantation rates, reduces \nthe risk of miscarriage, and increases the likelihood of a \nhealthy, full-term pregnancy. By enabling more precise \nembryo selection, PGT-A enhances both the efficiency \nand the emotional outcome of IVF cycles.\nPreimplantation genetic testing for aneuploidy (PGT-\nA) is a strategy used in IVF to select euploid embryos \nfor transfer, aiming to improve outcomes for couples \nwith advanced maternal age, recurrent miscarriage, or \nimplantation failure. However, its clinical benefit is highly \ndebated, as evidence on its ability to improve cumulative \nlive birth rates is conflicting and appears to be influenced \nby maternal age and ovarian response. Furthermore, \ntechnical limitations, such as the inability to detect \nsmall chromosomal abnormalities and the potential for \nFig. 2 Female infertility disorders and ART interventions. Illustrates common female infertility conditions: fallopian tube blockage, endometriosis, \npremature ovarian failure, polycystic ovary syndrome (PCOS), uterine fibroids, and cervical cancer. Highlights how these disorders disrupt natural \nconception and often require ART interventions like IVF for a successful pregnancy\n\nPage 5 of 15\nHussain et al. Middle East Fertility Society Journal           (2025) 30:44 \n \nmisclassifying certain ploidy states, present significant \nchallenges to its diagnostic accuracy [46].\nEmbryo culture and vitrification\nRecent advancements in embryo culture systems have \nsignificantly improved outcomes for both male and \nfemale gametes, optimizing the developmental potential \nof embryos prior to transfer (Fig.  5) [47]. These culture \nmedia now better mimic the natural uterine environ -\nment, supporting embryo growth from zygote to blasto -\ncyst stage. For male-factor infertility, specialized media \ncan enhance sperm-derived embryo quality, while for \nfemale patients, improved formulations address age-\nrelated oocyte deficiencies.\nThe development of vitrification has been equally \ntransformative for both sexes’ reproductive cells [48]. \nThis ultra-rapid freezing technique preserves not only \noocytes and embryos but also sperm and testicular tis -\nsue with minimal cellular damage. The method’s effec -\ntiveness has expanded fertility preservation options, \nallowing cancer patients of both genders to safeguard \ntheir reproductive potential before undergoing gonado -\ntoxic treatments [49].\nFor men, testicular tissue cryopreservation offers \nhope when sperm cannot be obtained via ejaculation, \nwhile women benefit from both oocyte and ovarian \ntissue [50]. These technologies now enable same-sex \ncouples and individuals facing medical challenges to \npursue biological parenthood. The combination of opti -\nmized culture conditions and reliable cryopreservation \nhas elevated IVF success rates globally, while support -\ning emerging applications like fertility extension for \ntransgender individuals undergoing hormonal thera -\npies [51].\nFig. 3 Scheme illustrating in vitro and in vivo fertilization. Controlled ovarian stimulation (COS) is used to promote follicle growth, maturation, \nand ovulation. ART adopts either IVF or ICSI for fertilization. Following fertilization, the preimplantation embryo is cultured in incubators, \nwhere suboptimal culture conditions such as pH, oxygen, temperature, and osmolality may affect its further development. Finally, \nthe 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 \ngametes interact together, and the sperm fertilizes the oocyte in the infundibulum. Next, the developing embryo moves towards the uterus \ninteracting with the female reproductive system in a physiologic and optimal environment\n\nPage 6 of 15Hussain et al. Middle East Fertility Society Journal           (2025) 30:44 \nLooking ahead, research continues to refine these \nsystems, with investigations into personalized culture \nmedia tailored to individual patients’ metabolic needs \nand AI-driven embryo selection algorithms that fur -\nther improve implantation rates [52]. These innovations \nunderscore how modern reproductive technologies \nincreasingly serve diverse populations while pushing \nthe boundaries of fertility science.\nArtificial intelligence (AI) and machine learning in IVF\nThe integration of artificial intelligence (AI) and machine \nlearning [53] into in vitro fertilization (IVF) protocols has \nFig. 4 Preimplantation genetic testing. After fertilization via IVF/ICSI, embryos are cultured and undergo cell/embryobiopsy for genetic analysis. This \ntesting identifies chromosomal or genetic abnormalities. Genetically normal embryos are then selected for uterine transfer to improve implantation \nsuccess\nFig. 5 Freezing and vitrification of embryo. This diagram depicts the process of IVF embryo selection and freezing. After embryos are retrieved \nduring IVF treatment, the high‑quality ones are identified through verification. Some embryos may be transferred immediately, while others are \npreserved through cryopreservation. The frozen embryos are later thawed and used for a delayed transfer, allowing for better timing and improved \nsuccess rates\n\nPage 7 of 15\nHussain et al. Middle East Fertility Society Journal           (2025) 30:44 \n \nrevolutionized multiple aspects of assisted reproductive \ntechnology, significantly enhancing precision and success \nrates [54]. One of the most impactful applications lies in \nembryo selection, where AI-driven algorithms analyze \nhigh-resolution time-lapse microscopy (TLM) images \nto assess morphological and morphokinetic parameters. \nThese systems evaluate cleavage patterns, blastocyst for -\nmation kinetics, and cellular symmetry, outperforming \ntraditional manual grading in predicting implantation \npotential [55].\nBeyond embryo assessment, AI has demonstrated \nremarkable utility in personalizing ovarian stimula -\ntion protocols. Advanced predictive models process \nmulti-parametric patient data—including age, hormonal \nprofiles, antral follicle count, and genetic markers—to \nforecast individual response to gonadotropins [56]. Such \ntools empower clinicians to optimize medication dos -\nages, minimizing risks of ovarian hyperstimulation syn -\ndrome (OHSS) while maximizing oocyte yield.\nEmerging applications extend to sperm selection, \nwhere convolutional neural networks (CNNs) identify \nspermatozoa with optimal DNA integrity and motil -\nity patterns, and endometrial receptivity analysis, where \ndeep learning interprets transcriptomic signatures to \npinpoint the ideal window for embryo transfer [57]. The \nconvergence of big data analytics and AI is further ena -\nbling the development of decision-support systems that \nintegrate electronic medical records with real-time labo -\nratory metrics to guide clinical judgments [58].\nWhile these technologies promise to reduce subjec -\ntivity in IVF, challenges persist regarding algorithmic \ntransparency, dataset diversity, and regulatory standardi -\nzation [59]. Future directions include federated learn -\ning approaches to improve model generalizability across \nethnic populations and the incorporation of multi-omics \ndata (proteomic, metabolomic) for holistic embryo via -\nbility assessments [60]. As validation studies proliferate, \nAI stands poised to transition from an adjunct tool to a \ncornerstone of precision reproductive medicine [61].\nEmerging techniques and future directions\nThe female reproductive microbiome in infertility \ndiagnosis and treatment\nRecent studies have highlighted that the female repro -\nductive tract hosts specialized microbial communities \nessential for fertility [62]. A healthy vaginal microbiome \nis dominated by Lactobacillus (70–95%), maintaining a \nprotective acidic environment, while dysbiosis (< 50% \nLactobacillus with overgrowth of Gardnerella or Prevo -\ntella) increases risks of infection and preterm birth [63]. \nThe cervix relies on Lactobacillus (60–80%) for mucosal \ndefense, with pathogenic overgrowth impairing sperm \nsurvival. Even the endometrium requires balanced \nmicrobiota (optimal 30–60% Lactobacillus) for embryo \nimplantation—dysbiosis here causes chronic inflam -\nmation and implantation failure [64]. Gut microbiome \nimbalances additionally disrupt hormonal regulation, \nexacerbating conditions like PCOS [65]. Throughout the \nreproductive tract, microbial disturbances contribute to \ninfertility via inflammation, immune dysfunction, and \ndirect interference with reproductive processes, high -\nlighting the microbiome’s critical role in female fertility \n(Fig. 6) [66].\nGene editing the future of fertility treatment: CRISPR‑Cas9 \nAdvance\nCRISPR-Cas9 gene editing has emerged as a ground -\nbreaking strategy for addressing genetic causes of infer -\ntility, offering precise correction of mutations that impair \nreproductive function (Fig.  7) [67]. Recent studies high -\nlight its success in restoring fertility in preclinical models \nby targeting key genes such as SYCP3, which is crucial for \nmeiotic recombination in oocytes, and AURKC , essential \nfor proper sperm head formation [68]. In female infertil -\nity, CRISPR has shown potential to rescue FIGLA muta -\ntions responsible for primordial follicle depletion, while \nin male infertility cases, it can correct CFTR variants \nunderlying obstructive azoospermia [69]. Research has \nalso demonstrated CRISPR’s ability to reverse epigenetic \nsilencing of LINE-1 retrotransposons in aged oocytes, \nrestoring their developmental competence [70]. While \nchallenges like off-target effects and efficient delivery \nto gonadal tissues persist, innovations in nanoparticle-\nbased delivery systems and ex vivo gamete editing tech -\nniques are accelerating clinical translation [71]. This \ntechnology not only enhances our understanding of \ninfertility’s genetic basis but also paves the way for per -\nsonalized therapies, potentially revolutionizing assisted \nreproductive technologies [71].\nStem cell applications in infertility treatment\nAlthough significant progress has been made in ART, \nmany couples are still unable to have healthy biologi -\ncal children without gamete donation or adoption [72]. \nInfertility caused by gamete deficiencies due to genetic \ndefects often remains unaffected by ART [73]. Most \ncouples, however, seek treatments that enable the birth \nof genetically related children through less invasive and \nmore cost-effective methods. In this regard, stem cell \ntherapies offer new hope, as shown in various experimen-\ntal preclinical and clinical models [74].\nStem cells, found in embryos and adult tissues, have \nthe ability to self-renew and differentiate when needed \n[75]. In fully developed organs, they help restore func -\ntion by repairing damage. Stem cells are categorized \nbased on their origin into embryonic stem cells (ESCs), \n\nPage 8 of 15Hussain et al. Middle East Fertility Society Journal           (2025) 30:44 \nadult stem cells (including mesenchymal stem cells, \nMSCs), induced pluripotent stem cells (iPSCs), sper -\nmatogonial stem cells (SSCs), and ovarian stem cells \n[76]. The process has been illustrated in Fig. 8 .\nPsychosocial impact of infertility\nPsychological and emotional distress\nInfertility can be a deeply distressing experience, with \nemotional impacts that extend far beyond the clinical \nFig. 6 Schematic representation of the female reproductive microbiome and its impact on fertility. A Healthy state: The vaginal, cervical, \nand endometrial microbiomes are predominantly populated by Lactobacillus species (depicted in blue), which maintain a protective \nacidic environment and support reproductive health. B Dysbiotic state: A shift in the microbial composition, characterized by a reduction \nin beneficial Lactobacillus and an overgrowth of pathogenic bacteria such as Gardnerella and Prevotella (depicted in red and orange), creates \na pro‑inflammatory environment. This dysbiosis is associated with adverse outcomes including implantation failure, preterm birth, and conditions \nlike PCOS, which can be influenced by gut microbiome imbalances (illustrated on the left)\nFig. 7 Embryo gene editing and transfer process. This figure shows the process of embryo gene modification starting with IVF or ICSI. Embryos \nundergo gene editing through techniques like microinjection or electroporation. After modification and biopsy, selected embryos are allowed \nto develop and are then transferred to the uterus\n\nPage 9 of 15\nHussain et al. Middle East Fertility Society Journal           (2025) 30:44 \n \naspects of treatment. Research shows that psychologi -\ncal distress, including anxiety, depression, and feelings \nof hopelessness, is common among individuals undergo -\ning ART (Fig. 9) [77]. A longitudinal study in 2023 found \nthat almost 50% of women undergoing IVF reported \nexperiencing significant emotional distress, which can \nnegatively affect their mental health and relationship \ndynamics [78].\nMoreover, the emotional toll of infertility can have a \ndetrimental effect on treatment outcomes. Studies sug -\ngest that stress and emotional distress can lower the \nchances of successful pregnancies through IVF [79]. \nTherefore, psychological support is critical in optimizing \nboth emotional well-being and treatment success.\nCoping mechanisms and social support\nMany individuals undergoing infertility treatments rely \non various coping strategies to manage their emotional \ndistress. Cognitive-behavioral therapy (CBT), mindful -\nness meditation, and participation in support groups \nhave been shown to reduce stress and improve psy -\nchological outcomes for couples [80]. Fertility-specific \ncounseling and therapy can help individuals and couples \nnavigate the emotional journey of infertility, supporting \nmental health and improving overall treatment satisfac -\ntion [81].\nSupport groups, both in-person and online, provide a \nplatform for individuals to share experiences and receive \nemotional support from others facing similar struggles \nFig. 8 Stem cell reprogramming pathway for generating fertile germ cells.This schematic illustrates the stepwise conversion of adult somatic \ncells (fibroblasts/blood cells) into functional germ cells through an iPSC intermediate. Key stages include (1) somatic cell reprogramming \nusing Yamanaka factors (OCT‑4/KLF4), (2) primordial germ cell induction via cytokine signaling, and (3) differentiation into fertilizable oocyte/\nspermatid‑like cells to overcome genetic infertility\n\nPage 10 of 15Hussain et al. Middle East Fertility Society Journal           (2025) 30:44 \n[82]. Professional counseling, including couples therapy, \nhas been shown to improve coping mechanisms, reduce \nrelationship strain, and enhance emotional resilience \nduring ART cycles [83].\nSocial stigma and cultural barriers\nThe global stigma of infertility\nInfertility carries significant social stigma in many cul -\ntures, often leading individuals to experience shame, \nguilt, and isolation due to their inability to conceive [84]. \nIn many societies, parenthood is closely tied to per -\nsonal identity, marital stability, and social status, mak -\ning infertility a highly sensitive issue [85]. This stigma is \nparticularly pronounced in regions such as South Asia, \nsub-Saharan Africa, and parts of the Middle East, where \nchildbearing is deeply interwoven with cultural and \nfamilial expectations [86]. Women, in particular, bear \nthe brunt of infertility stigma, often facing discrimina -\ntion, exclusion, and even divorce or abandonment due \nto their inability to conceive [87]. The burden of infertil -\nity stigma extends beyond the personal level, influencing \nhealthcare-seeking behaviors, delaying medical interven -\ntion, and exacerbating emotional distress among affected \nindividuals [88].\nThe psychological and social consequences of infertility \nstigma\nThe stigma associated with infertility often results in \nsevere psychological distress, including anxiety, depres -\nsion, and low self-esteem [89]. Many individuals report \nfeeling a loss of purpose, social alienation, and dimin -\nished self-worth due to their inability to fulfill soci -\netal and familial expectations of parenthood [90]. In \npatriarchal societies, women are frequently blamed for \ninfertility, even when male factor infertility is a signifi -\ncant contributor to childlessness [91]. This blame can \nlead to emotional and physical abuse, social isolation, \nand diminished quality of life. The pressure to conceive \nmay also strain relationships, causing marital discord \nand leading to emotional withdrawal between part -\nners [92]. Additionally, the stigma surrounding infer -\ntility often deters individuals from openly discussing \ntheir struggles or seeking medical assistance. Many \nfear judgment from family, friends, and even healthcare \nproviders, leading to delayed diagnosis and treatment \n[93]. The lack of open conversations about infertility in \ncertain cultures reinforces misinformation and miscon -\nceptions, further marginalizing those affected [94].\nFig. 9 The complex interplay of factors influencing infertility. This figure outlines factors contributing to infertility, categorized into lifestyle, \ngenetic, and psycho‑social‑economic dimensions. It highlights modifiable risks like obesity and smoking, genetic disorders, and the psychological \nand socio‑economic impacts such as depression and relationship strain. These factors emphasize infertility as a complex interplay of physical, \ngenetic, and emotional elements\n\nPage 11 of 15\nHussain et al. Middle East Fertility Society Journal           (2025) 30:44 \n \nCultural and religious influences on infertility perceptions\nCultural and religious beliefs play a significant role in \nshaping societal attitudes toward infertility [95]. In many \ntraditional societies, infertility is often viewed as divine \npunishment, karma, or the result of past sins [96]. Such \nbeliefs can reinforce stigma, discouraging couples from \nseeking medical interventions such as assisted repro -\nductive technologies (ART). In contrast, some religious \ncommunities have gradually begun to accept ART, recog-\nnizing the role of medical science in overcoming infertil -\nity while adhering to ethical and moral guidelines [97]. \nThe degree of acceptance, however, varies widely, and in \nmany cultures, ART remains inaccessible or stigmatized \ndue to religious constraints and ethical concerns [98].\nAddressing infertility stigma through education \nand awareness\nPublic education and awareness campaigns are crucial \nin reducing the stigma surrounding infertility. Provid -\ning accurate information about infertility, its causes, and \navailable treatments can help dispel myths and encour -\nage a more supportive and understanding society [99]. \nMedia, healthcare professionals, and advocacy organiza -\ntions play a key role in normalizing conversations around \ninfertility and promoting reproductive health education. \nInvolving community and religious leaders in discussions \non infertility can also facilitate cultural shifts toward \ngreater acceptance and support for affected individuals \n[100].\nIntegrating psychological support in infertility care\nHealthcare providers must adopt a holistic approach \nthat integrates psychological support into infertility care. \nCounseling services, peer support groups, and mental \nhealth interventions can help individuals cope with the \nemotional burden of infertility [101]. Cognitive-behav -\nioral therapy (CBT), mindfulness techniques, and fer -\ntility counseling have been shown to reduce stress and \nimprove psychological resilience among patients under -\ngoing fertility treatments [6]. Providing accessible and \nculturally sensitive mental health services can help indi -\nviduals navigate the emotional challenges of infertility \nwhile mitigating the negative effects of societal stigma as \nthe guidelines provided by the ESHERE manual (Fig.  10) \n[102, 103].\nEncouraging policy and institutional support\nGovernments and healthcare institutions have a role to \nplay in reducing infertility stigma by ensuring that repro -\nductive health services are accessible, affordable, and \ninclusive [104]. Policies that promote insurance coverage \nfor fertility treatments, workplace accommodations for \nindividuals undergoing ART, and mental health support \nin fertility clinics can contribute to a more supportive \nenvironment [105]. In addition, legal protections against \ndiscrimination based on infertility status can help safe -\nguard the rights of affected individuals, ensuring that \nthey do not face workplace bias, social exclusion, or une -\nqual access to healthcare.\nFig. 10 Visual guide outlining a stage‑specific psychosocial care protocol for infertility and ART, customized to individual patient requirements\n\nPage 12 of 15Hussain et al. Middle East Fertility Society Journal           (2025) 30:44 \nConclusion\nThe field of infertility treatment has witnessed remark -\nable progress through assisted reproductive technolo -\ngies (ART), yet significant challenges remain. Over \nrecent decades, innovations such as IVF/ICSI, preim -\nplantation genetic testing, and vitrification techniques \nhave dramatically improved success rates, offering hope \nto millions of couples worldwide. These technological \nadvancements now enable clinicians to address previ -\nously untreatable causes of infertility, from severe male \nfactor infertility to age-related ovarian decline. The \nintegration of artificial intelligence for embryo selec -\ntion and emerging gene editing technologies promises \nto further enhance treatment precision and outcomes \nin the coming years.\nHowever, the emotional and psychological burdens \nassociated with infertility continue to pose substan -\ntial challenges for patients and clinicians alike. Despite \ntechnological progress, the infertility journey remains \nfraught with stress, anxiety, and profound emotional \nupheaval. Studies consistently show that 30–50% of \nART patients experience clinically significant psycho -\nlogical distress [106–108], which may negatively impact \ntreatment adherence and outcomes. The cyclical nature \nof ART treatment—with its alternating periods of hope \nand disappointment—creates unique mental health chal -\nlenges that demand specialized support services and \ninterventions.\nMoving forward, the field must prioritize three key \nareas to optimize patient care. First, continued research \ninto personalized treatment approaches through AI and \nmulti-omics technologies will be crucial for improving \nsuccess rates while minimizing risks. Second, addressing \ndisparities in access to care remains an ethical impera -\ntive, particularly for costly emerging therapies like stem \ncell applications and fertility preservation. Finally, and \nperhaps most importantly, the integration of psychoso -\ncial support must become standard practice in fertility \nclinics worldwide. This includes routine mental health \nscreening, counseling services, and support groups to \nhelp patients navigate the complex emotional terrain of \ninfertility treatment.\nUltimately, the most effective infertility care will har -\nmonize cutting-edge reproductive technologies with \ncomprehensive psychosocial support. By addressing \nboth the biological and emotional dimensions of infer -\ntility, clinicians can provide truly patient-centered care \nthat optimizes both clinical outcomes and quality of life. \nAs research continues to push the boundaries of repro -\nductive medicine, maintaining this balanced, holistic \napproach will be essential for meeting the diverse needs \nof individuals and couples facing infertility. The future \nof infertility treatment lies not just in technological \ninnovation, but in our ability to integrate these advances \nwith compassionate, whole-person care.\nAbbreviations\nART   Assisted reproductive technologies\nIVF  In vitro fertilization\nICSI  Intracytoplasmic sperm injection\nPGT‑A  Preimplantation genetic testing for aneuploidy\nPGT‑M  Preimplantation genetic testing for monogenic disorders\nCBT  Cognitive ‑behavioral therapy\nAI  Artificial intelligence\nIVA  In vitro activation\nCRISPR  Clustered regularly interspaced short palindromic repeats\nMACS  Magnetic‑activated cell sorting\nTESE  Testicular sperm extraction\nPCOS  Polycystic ovary syndrome\nOHSS  Ovarian hyperstimulation syndrome\nAuthors’ contributions\nA.H., and M.A., have gathered data, outlined and finalized the initial manu‑\nscript draft. G.M., M.L., Z.U.A., Y.R., A.M., and A.U., helped to analyze data. M.H.L., \nprovided revisions and finalized the manuscript. All authors have reviewed \nand approved the final manuscript.\nFunding\nNot applicable.\nData availability\nThe authors confirm that all the data have already been presented in the \narticle.\nDeclarations\nEthics approval and consent to participate\nNot applicable.\nConsent for publication\nAfter reviewing the manuscript, the authors have decided to submit it for \npublication. The authors declare that nothing in the study has ever been pub‑\nlished before or is presently being considered for publication anywhere.\nCompeting interests\nThe authors declare no competing interests.\nReceived: 9 May 2025   Accepted: 18 September 2025\nReferences\n 1. Hussain A et al (2025) A novel homozygous splicing mutation in \nAK7 causes multiple morphological abnormalities of sperm flagella \nin patients from consanguineous Pakistani families. Asian J Androl \n27(2):189–195\n 2. Fisher JR, Hammarberg K (2011) Psychological and social aspects of \ninfertility in men: an overview of the evidence and implications for psy‑\nchologically informed clinical care and future research. Asian J Androl \n14(1):121\n 3. Hasanpoor‑Azghdy SB, Simbar M, Vedadhir A (2014) The emotional‑psy‑\nchological consequences of infertility among infertile women seeking \ntreatment: results of a qualitative study. Iran J Reprod Med 12(2):131\n 4. Peterson B, Place JMS (2019) The experience of infertility: an unex‑\npected barrier in the transition to parenthood. In: Taubman – Ben‑Ari, \nO. (eds) Pathways and Barriers to Parenthood. Cham: Springer. https:// \ndoi. org/ 10. 1007/ 978‑3‑ 030‑ 24864‑2_2\n 5. Schoebi D, Randall AK (2015) Emotional dynamics in intimate relation‑\nships. Emot Rev 7(4):342–348\n\nPage 13 of 15\nHussain et al. Middle East Fertility Society Journal           (2025) 30:44 \n \n 6. Vioreanu A‑M (2021) The psychological impact of infertility. Directions \nfor the development of interventions. Ment Health 4(1):22–37\n 7. Tenchov R, QA Zhou (2025) Assisted reproductive technology: a ray of \nhope for infertility. ACS Omega 23;10(22):22347–22365\n 8. Sciorio R, Esteves SC (2020) Clinical utility of freeze‑all approach in ART \ntreatment: a mini‑review. Cryobiology 92:9–14\n 9. Applegarth LD (2009) Psychological issues of infertility and assisted \nreproductive technology. In Book: Infertility in the Male, p. 516–527. \nhttps:// doi. org/ 10. 1017/ CBO97 80511 635656. 031\n 10. del Arco Paz A et al (2024) Advancements and challenges in preimplan‑\ntation genetic testing for aneuploidies: in the pathway to non‑invasive \ntechniques. Genes 15(12):1613\n 11. Van de Wiel L (2022) Disrupting the biological clock: fertility benefits, \negg freezing and proactive fertility management. Reproductive Bio‑\nmedicine & Society Online 14:239–250\n 12. Sax MR, Lawson AK (2022) Emotional support for infertility patients: \nintegrating mental health professionals in the fertility care team. \nWomen 2(1):68–75\n 13. Hamid OAO et al (2024) Female infertility associated depression and \nanxiety: a comprehensive review. Metall Mater Eng 30(4):370–380\n 14. Brannigan RE, Fantus RJ, Halpern JA (2021) Fertility preservation in men: \na contemporary overview and a look toward emerging technologies. \nFertil Steril 115(5):1126–1139\n 15. Dolmans MM, Manavella DD (2019) Recent advances in fertility preser‑\nvation. J Obstet Gynaecol Res 45(2):266–279\n 16. Inhorn MC, Patrizio P (2015) Infertility around the globe: new thinking \non gender, reproductive technologies and global movements in the \n21st century. Hum Reprod Update 21(4):411–426\n 17. Sharma A, Shrivastava D (2022) Psychological problems related to \ninfertility. Cureus 14(10):e30320. https:// doi. org/ 10. 7759/ cureus. 30320\n 18. Meis LA (2013) Couple and family involvement in adult mental health \ntreatment: a systematic review. Clin Psychol Rev 33(2):275–286\n 19. Li A et al (2025) Considerations on optimizing the patient experience \nduring assisted reproductive technology treatment: a qualitative analy‑\nsis. F&S Reports. https:// doi. org/ 10. 1016/j. xfre. 2025. 01. 002\n 20. Bishop MS (2022) A toolkit of one’s own: a depth psychological and \ncreative approach to treating infertile women. Human Infertility \n30;38(6):1324–1333\n 21. Graham ME (2023) Assisted reproductive technology: short‑and long‑\nterm outcomes. Dev Med Child Neurol 65(1):38–49\n 22. Gupta K, Rajalakshmi Walavalkar DKU, (2020) Male infertility. In: TOG \nALGORITHMS–4, : p. 33‑42. https:// www. fogsi. org/ wp‑ conte nt/ uploa ds/ \n2024/ 11/ TOG_4_ Algor ithm_ Bookl et. pdf\n 23. Bieth E, Hamdi SM, Mieusset R (2021) Genetics of the congenital \nabsence of the vas deferens. Hum Genet 140(1):59–76\n 24. Roychoudhury S et al (2021) Environmental factors‑induced oxidative \nstress: hormonal and molecular pathway disruptions in hypogonadism \nand erectile dysfunction. Antioxidants 10(6):837\n 25. Nyboe Andersen A, Carlsen E, Loft A (2008) Trends in the use of intra‑\ncytoplasmatic sperm injection marked variability between countries. \nHum Reprod Update 14(6):593–604\n 26. Shah R, Gupta C (2018) Advances in sperm retrieval techniques in \nazoospermic men: a systematic review. Arab J Urol 16(1):125–131\n 27. Pacheco A (2020) Magnetic‑activated cell sorting (MACS): a useful \nsperm‑selection technique in cases of high levels of sperm DNA frag‑\nmentation. J Clin Med 9(12):3976\n 28. Du R‑Q et al (2023) A review of pre‑implantation genetic testing tech‑\nnologies and applications. Reproductive and Developmental Medicine \n7(01):20–31\n 29. Zhang X et al (2024) Emerging trends in sperm selection: enhancing \nsuccess rates in assisted reproduction. Reprod Biol Endocrinol 22(1):67\n 30. Lok IH (2002) Psychiatric morbidity amongst infertile Chinese women \nundergoing treatment with assisted reproductive technology and the \nimpact of treatment failure. Gynecol Obstet Invest 53(4):195–199\n 31. Verhaak CM (2007) Women’s emotional adjustment to IVF: a systematic \nreview of 25 years of research. Hum Reprod Update 13(1):27–36\n 32. Ikemoto Y (2021) Analysis of severe psychological stressors in women \nduring fertility treatment: Japan‑Female Employment and Mental \nhealth in Assisted reproductive technology (J‑FEMA) study. Arch \nGynecol Obstet 304(1):253–261\n 33. de Castro MHM (2021) Psychosocial aspects of gestational grief in \nwomen undergoing infertility treatment: a systematic review of \nqualitative and quantitative evidence. Int J Environ Res Public Health. \nhttps:// doi. org/ 10. 3390/ ijerp h1824 13143\n 34. Unuane D et al (2011) Endocrine disorders & female infertility. Best \nPract Res Clin Endocrinol Metab 25(6):861–873\n 35. Concepción‑Zavaleta MJ et al (2023) Endocrine factors associated \nwith infertility in women: an updated review. Expert Rev Endocrinol \nMetab 18(5):399–417\n 36. Goyri E, Kohls G, Garcia‑ Velasco J (2024) IVF stimulation protocols and \noutcomes in women with endometriosis. Best Pract Res Clin Obstet \nGynaecol 92:102429\n 37. Bühler N (2021) Ageing eggs, ageless mothers? Egg donation and \nthe extension of fertility, in When Reproduction Meets Ageing. Emer ‑\nald Publishing Limited. p. 129–156. https:// doi. org/ 10. 1016/j. rbms. \n2021. 07. 014\n 38. Tian Y et al (2024) Preimplantation genetic testing in the current era, \na review. Arch Gynecol Obstet 309(5):1787–1799\n 39. Vitale F, Dolmans M ‑M (2024) Comprehensive review of in vitro \nhuman follicle development for fertility restoration: recent achieve ‑\nments, current challenges, and future optimization strategies. J Clin \nMed 13(6):1791\n 40. Barrera N, Omolaoye TS, Du Plessis SS (2022) A contemporary view \non global fertility, infertility, and assisted reproductive techniques. \nFertility, Pregnancy, and Wellness. Elsevier, pp 93–120\n 41. Verma D et al (2022) History of human in‑ vitro fertilization (IVF) and \nassisted reproduction techniques (ART). International Journal of \nScientific Research in Modern Science and Technology 1(1):18–27\n 42. Iketubosin F (2018) In vitro fertilization embryo transfer processes \nand pathway: a review from practice perspective. Trop J Obstet \nGynaecol 35(3):227–232\n 43. Balen A (2022) Infertility in practice. CRC Press. https:// doi. org/ 10.  \n1201/ 97810 03094 951\n 44. Morales C (2024) Current applications and controversies in preim‑\nplantation genetic testing for aneuploidies (PGT ‑A) in in vitro fertiliza‑\ntion. Reprod Sci 31(1):66–80\n 45. Lee C‑I (2019) Performance of preimplantation genetic testing for \naneuploidy in IVF cycles for patients with advanced maternal age, \nrepeat implantation failure, and idiopathic recurrent miscarriage. \nTaiwan J Obstet Gynecol 58(2):239–243\n 46. Zhou F et al (2025) The clinical application and challenges of preim‑\nplantation genetic testing. Front Genet 16:1599088\n 47. Swain JE et al (2016) Optimizing the culture environment and \nembryo manipulation to help maintain embryo developmental \npotential. Fertil Steril 105(3):571–587\n 48. Schiewe MC, Anderson RE (2017) Vitrification: the pioneering past to \ncurrent trends and perspectives of cryopreserving human embryos, \ngametes and reproductive tissue. J Biorepos Sci Appl Med. https://  \ndoi. org/ 10. 2147/ BSAM. S1393 76\n 49. Michalczyk K, Cymbaluk ‑Płoska A (2021) Fertility preservation and \nlong‑term monitoring of gonadotoxicity in girls, adolescents and \nyoung adults undergoing cancer treatment. Cancers (Basel) 13(2):202\n 50. Onofre J (2016) Cryopreservation of testicular tissue or testicular \ncell suspensions: a pivotal step in fertility preservation. Hum Reprod \nUpdate 22(6):744–761\n 51. Rubin E, Palmor M, Amato P (2025) Reproductive health in trans and \ngender diverse patients: fertility treatment and preservation options \nfor transgender and gender diverse people. Reproduction. https://  \ndoi. org/ 10. 1530/ REP‑ 24‑ 0120\n 52. Hew Y et al (2024) Artificial intelligence in IVF laboratories: elevating \noutcomes through precision and efficiency. Biology 13(12):988\n 53. Tomlinson RL (2006) Cell cycle ‑regulated trafficking of human telom‑\nerase to telomeres. Mol Biol Cell 17(2):955–965\n 54. Wu Y‑C et al (2025) Artificial intelligence and assisted reproductive \ntechnology: a comprehensive systematic review. Taiwan J Obstet \nGynecol 64(1):11–26\n 55. Si K, Huang B, Jin L (2023) Application of artificial intelligence in \ngametes and embryos selection. Hum Fertil 26(4):757–777\n 56. Pacheco F, Arrach N (2024) Artificial intelligence in ovarian stimula‑\ntion. Reprod Biomed Online. https:// doi. org/ 10. 1016/j. rbmo. 2024. \n104513\n\nPage 14 of 15Hussain et al. Middle East Fertility Society Journal           (2025) 30:44 \n 57. Finnerty R (2024) The oviduct, sperm, and eggs: a multiomics ai \nintegrated in vivo characterization during pregnancy. PhD thesis \nUniversity of Missouri‑ Columbia. https:// mospa ce. umsys tem. edu/ \nxmlui/ bitst ream/ handle/ 10355/ 105885/ Finne rtyRy anRes earch. pdf? \nseque nce= 1& isAll owed=y\n 58. Khalifa M, Albadawy M, Iqbal U (2024) Advancing clinical decision \nsupport: the role of artificial intelligence across six domains. Comput \nMethods Programs Biomed Update 5:100142\n 59. Cohen J et al (2025) Artificial intelligence in assisted reproductive \ntechnology: separating the dream from reality. Reprod Biomed Online \n50(4):104855\n 60. Suura SR (2025) Integrating artificial intelligence, machine learning, and \nbig data with genetic testing and genomic medicine to enable earlier, \npersonalized health interventions. Deep Science Publishing. https:// doi. \norg/ 10. 70593/ 978‑ 93‑ 49307‑ 76‑6\n 61. Hanassab S (2024) The prospect of artificial intelligence to personalize \nassisted reproductive technology. NPJ Digit Med 7(1):55\n 62. Nakama C et al (2022) The continuum of microbial ecosystems along \nthe female reproductive tract: implications for health and fertility. \nPathogens 11(11):1244\n 63. Kramer M (2024) The vaginal microbiome in health and disease. Univer‑\nsity of Rijeka. Faculty of Medicine. urn:nbn:hr:184:035836\n 64. Bhattacharya K et al (2023) Reproductive tract microbiome and thera‑\npeutics of infertility. Middle East Fertil Soc J 28(1):11\n 65. He F‑F, Li Y‑M (2020) Role of gut microbiota in the development of \ninsulin resistance and the mechanism underlying polycystic ovary \nsyndrome: a review. J Ovarian Res 13(1):73\n 66. Wang N (2024) The effects of microbiota on reproductive health: a \nreview. Crit Rev Food Sci Nutr 64(6):1486–1507\n 67. Gürbüz T, Yurci A (2024) The intersection of technology and infertility: \npioneering approaches in genetic editing and artificial intelligence. \nJournal of Controversies in Obstetrics & Gynecology and Pediatrics \n2(3):64–68\n 68. Wei Y (2024) Genetic mechanisms of fertilization failure and early \nembryonic arrest: a comprehensive review. Hum Reprod Update \n30(1):48–80\n 69. Kalapahar S et al (2023) Overview of genetics in infertility. Bulletin of \nInstitute of Reproductive Medicine. 77(9):39–45\n 70. Kohlrausch FB et al (2022) Control of LINE‑1 expression maintains \ngenome integrity in germline and early embryo development. Reprod \nSci 29(2):328–340\n 71. Volodina O, Smirnikhina S (2025) The future of gene therapy: a review \nof in vivo and ex vivo delivery methods for genome editing‑based \ntherapies. Mol Biotechnol 67(2):425–437\n 72. Berntsen S (2019) The health of children conceived by ART:‘the chicken \nor the egg?’ Hum Reprod Update 25(2):137–158\n 73. Tahmasbpour E, Balasubramanian D, Agarwal A (2014) A multi‑faceted \napproach to understanding male infertility: gene mutations, molecular \ndefects and assisted reproductive techniques (ART). J Assist Reprod \nGenet 31:1115–1137\n 74. Saha S (2021) Application of stem cell therapy for infertility. Cells \n10(7):1613\n 75. Prochazkova M et al (2015) Embryonic versus adult stem cells. Stem cell \nbiology and tissue engineering in dental sciences. Elsevier, pp 249–262\n 76. Tian Z et al (2023) Introduction to stem cells. Prog Mol Biol Transl Sci \n199:3–32\n 77. Boivin J, Griffiths E, Venetis CA (2011) Emotional distress in infertile \nwomen and failure of assisted reproductive technologies: meta‑analysis \nof prospective psychosocial studies. BMJ. https:// doi. org/ 10. 1136/ bmj. \nd223\n 78. Wu L (2023) Psychological distress among women undergoing in vitro \nfertilization‑embryo transfer: a cross‑sectional and longitudinal network \nanalysis. Front Psychol 13:1095365\n 79. Zhou F‑J, Cai Y‑N, Dong Y‑Z (2019) Stress increases the risk of pregnancy \nfailure in couples undergoing IVF. Stress 22(4):414–420\n 80. Abdollahpour S (2022) The efficacy of cognitive behavioural therapy on \nstress, anxiety and depression of infertile couples: a systematic review \nand meta‑analysis. J Obstet Gynaecol 42(2):188–197\n 81. Banser S (2022) Navigating infertility treatment in Canada: a qualitative \nstudy of the experiences of female adult survivors of childhood cancer. \nUniversity of British Columbia. http:// hdl. handle. net/ 2429/ 81178\n 82. O’Connell SBL et al (2021) ‘I felt less alone knowing I could contribute \nto the forum’: psychological distress and use of an online infertility peer \nsupport forum. Health Psychol Behav Med 9(1):128–148\n 83. Brigance CA, Brown EC, Cottone RR (2021) Therapeutic intervention \nfor couples experiencing infertility: an emotionally focused couples \ntherapy approach. Fam J 29(1):72–79\n 84. Zou W, Tang L, Wallis C (2025) “My Body is Betraying Me”: exploring the \nstigma and coping strategies for infertility among women across ethnic \nand racial groups. Health Communication, p. 1–12. https:// doi. org/ 10. \n1080/ 10410 236. 2025. 24709 84\n 85. Guzzo KB, Hayford SR (2020) Pathways to parenthood in social and fam‑\nily contexts: decade in review, 2020. J Marriage Fam 82(1):117–144\n 86. Oseni K (2024) The lived experiences of nigerian women diagnosed \nwith infertility and residing in the United States. A PhD thesis Walden \nUniversity. https:// schol arwor ks. walde nu. edu/ disse rtati ons/ 15834/\n 87. Oyuyo C (2024) Psychological Impact of perceptions of infertility and \nchildlessness: a systematic literature review. California Southern Univer‑\nsity. https:// doi. org/ 10. 1177/ 03000 60520 932403\n 88. Farhat M (2024) Exploring health‑seeking behaviors and coping \nstrategies: a qualitative study of women in urban slum areas of Lahore, \nPakistan. Sociological Research And Innovation 2(1):01–21\n 89. Xie Y (2023) The impact of stigma on mental health and quality of life of \ninfertile women: a systematic review. Front Psychol 13:1093459\n 90. Gameiro S, Finnigan A (2017) Long‑term adjustment to unmet parent‑\nhood goals following ART: a systematic review and meta‑analysis. Hum \nReprod Update 23(3):322–337\n 91. Mumtaz Z, Shahid U, Levay A (2013) Understanding the impact of gen‑\ndered roles on the experiences of infertility amongst men and women \nin Punjab. Reprod Health 10:1–10\n 92. Pincus L (2023) Studies in emotional conflict and growth. In Book: Mar‑\nriage: Published by Taylor & Francis https:// doi. org/ 10. 4324/ 97810 03395 \n355\n 93. Klitzman R (2018) Impediments to communication and relationships \nbetween infertility care providers and patients. BMC Womens Health \n18:1–12\n 94. Novotny M (2023) Misconception fatigue: towards an embodied rheto‑\nric for infertility advocacy. Rhetor Rev 42(3):184–215\n 95. Widge A (2002) Sociocultural attitudes towards infertility and assisted \nreproduction in India. Current practices and controversies in assisted \nreproduction 60:74\n 96. Wang F (2024) A comparison of human life in Christian and Chinese \nBuddhist bioethics. Religions 15(5):624\n 97. Serour GI, Serour AG (2017) Ethical issues in infertility. Best Pract Res Clin \nObstet Gynaecol 43:21–31\n 98. Rizk BR et al (2010) Religious perspectives of ethical issues in infertility \nand art. Infertility and assisted reproduction, p. 728–746 https:// sa1s3. \npatie ntpop. com/ assets/ docs/ 190744. pdf\n 99. Ali S et al (2011) Knowledge, perceptions and myths regarding infertil‑\nity among selected adult population in Pakistan: a cross‑sectional study. \nBMC Public Health 11:1–7\n 100. Tohit NFM, Haque M (2024) Forbidden conversations: a comprehen‑\nsive exploration of taboos in sexual and reproductive health. Cureus \n16(8):e66723. https:// doi. org/ 10. 7759/ cureus. 66723\n 101. Wischmann T (2008) Implications of psychosocial support in infertility–\na critical appraisal. J Psychosom Obstet Gynecol 29(2):83–90\n 102. Kaplan DA (2024) Culturally responsive reproductive mental health \npractice: pitfalls and possibilities. cultural responsiveness in assisted \nreproductive technology: best practices for clinics and affiliated provid‑\ners. Springer, pp 295–312\n 103. Gameiro S et al (2015) ESHRE guideline: routine psychosocial care in \ninfertility and medically assisted reproduction‑a guide for fertility staff. \nHum Reprod 30(11):2476–2485\n 104. Zhang L, Qiao D (2025) Perceptions of health system professionals \non integrating fertility care into reproductive health policy in China. \nHealthcare 13(5):555. https:// doi. org/ 10. 3390/ healt hcare 13050 555\n 105. Adamson GD et al (2024) Policy solutions to improve access to fertility \ntreatment and optimise patient care: Consensus from an expert forum \nhttps:// www. organ on. com/ wp‑ conte nt/ uploa ds/ sites/2/ 2024/ 07/ \nAccess‑ to‑ ferti lity‑ treat ment‑ white‑ paper‑ CRA‑ Organ on‑ rev‑ 07‑ 01‑ 24. \npdf\n\nPage 15 of 15\nHussain et al. Middle East Fertility Society Journal           (2025) 30:44 \n \n 106. Gameiro S (2012) Why do patients discontinue fertility treatment? A \nsystematic review of reasons and predictors of discontinuation in fertil‑\nity treatment. Hum Reprod Update 18(6):652–669\n 107. Verhaak CM (2007) Long‑term psychological adjustment to IVF/ICSI \ntreatment in women. Hum Reprod 22(1):305–308\n 108. Matthiesen SM (2011) Stress, distress and outcome of assisted \nreproductive technology (ART): a meta‑analysis. Hum Reprod \n26(10):2763–2776\nPublisher’s Note\nSpringer Nature remains neutral with regard to jurisdictional claims in pub‑\nlished maps and institutional affiliations.","source_license":"CC0","license_restricted":false}