Critical Considerations and Contemporary Solutions in IVF Management of Women with Endometriosis

In: Endometriosis - Medical Aspects and Modern Approaches [Working Title] · 2026 · doi:10.5772/intechopen.1015342 · W7160510572
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This paper reviews the inflammatory and oxidative mechanisms by which endometriosis negatively impacts ovarian function and endometrial receptivity, thereby affecting IVF outcomes, and discusses individualized management strategies.

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This paper reviews contemporary, evidence-based explanations and management considerations for infertility in women with endometriosis, focusing on how inflammation and oxidative stress affect the ovarian microenvironment, oocyte/embryo development, endometrial receptivity, and tubal factors relevant to IVF. It synthesizes that endometriomas can create proinflammatory and prooxidative follicular conditions (including cytokines, reactive oxygen species, and iron-related oxidative damage) that may reduce oocyte numbers and compromise oocyte maturation, while available data do not show a consistent increase in embryo genetic abnormalities, with limitations that heterogeneity across disease severity and ovarian reserve complicates interpretation. The paper also highlights progesterone resistance and receptivity marker alterations (e.g., HOXA10, LIF, integrins) as implantation barriers, and stresses that endometriosis-associated hydrosalpinx can be asymptomatic yet negatively affect implantation, making pre-transfer tubal evaluation important. This paper is centrally about endometriosis — it specifically analyzes mechanisms and IVF management factors such as endometrioma-related ovarian effects, endometrial receptivity/progesterone resistance, and hydrosalpinx.

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Abstract

Endometriosis is a chronic inflammatory disorder characterized by persistent inflammation and increased oxidative stress at both ovarian and endometrial levels, affecting fertility through mechanisms that extend beyond anatomical distortion alone. In the presence of endometrioma, the follicular microenvironment may be enriched with proinflammatory cytokines and reactive oxygen species, which can impair granulosa cell function and mitochondrial activity, ultimately compromising oocyte development and competence. Clinically, this may manifest as a reduced number of retrieved oocytes and fewer embryos available for transfer. However, current evidence does not indicate a consistent detrimental effect on embryo genetic competence, although lower embryo numbers and less favorable morphological features have been reported in some patient groups. In many cases, diminished ovarian reserve, rather than intrinsic impairment of embryo genetic integrity, appears to be the primary factor limiting in vitro fertilization (IVF) outcomes. At the endometrial level, progesterone resistance and altered receptivity-related pathways may further compromise implantation. Hydrosalpinx, which may arise as a consequence of chronic pelvic inflammation and tubal damage, represents an additional and often underrecognized factor. Because it may remain asymptomatic, careful evaluation before embryo transfer is essential given its known negative impact on implantation. Beyond local pelvic effects, systemic inflammatory and oxidative processes may also influence ovarian tissue and the follicular environment. Modifiable lifestyle factors, including nutrition, sleep, and oxidative stress balance, while not primary determinants of IVF success, may contribute to a more supportive reproductive environment. This chapter reviews these mechanisms and their clinical implications, with particular emphasis on individualized IVF management and emerging regenerative approaches.
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Abstract

Endometriosis is a chronic inflammatory disorder characterized by persistent inflammation and increased oxidative stress at both ovarian and endometrial levels, affecting fertility through mechanisms that extend beyond anatomical distortion alone. In the presence of endometrioma, the follicular microenvironment may be enriched with proinflammatory cytokines and reactive oxygen species, which can impair granulosa cell function and mitochondrial activity, ultimately compromising oocyte development and competence. Clinically, this may manifest as a reduced number of retrieved oocytes and fewer embryos available for transfer. However, current evidence does not indicate a consistent detrimental effect on embryo genetic competence, although lower embryo numbers and less favorable morphological features have been reported in some patient groups. In many cases, diminished ovarian reserve, rather than intrinsic impairment of embryo genetic integrity, appears to be the primary factor limiting in vitro fertilization (IVF) outcomes. At the endometrial level, progesterone resistance and altered receptivity-related pathways may further compromise implantation. Hydrosalpinx, which may arise as a consequence of chronic pelvic inflammation and tubal damage, represents an additional and often underrecognized factor. Because it may remain asymptomatic, careful evaluation before embryo transfer is essential given its known negative impact on implantation. Beyond local pelvic effects, systemic inflammatory and oxidative processes may also influence ovarian tissue and the follicular environment. Modifiable lifestyle factors, including nutrition, sleep, and oxidative stress balance, while not primary determinants of IVF success, may contribute to a more supportive reproductive environment. This chapter reviews these mechanisms and their clinical implications, with particular emphasis on individualized IVF management and emerging regenerative approaches.

Keywords

- endometriosis - IVF outcomes - infertility - hydrosalpinx - surgical management - lifestyle modification 1. Introduction Endometriosis is among the most prevalent chronic inflammatory gynecological conditions in women of reproductive age, affecting an estimated 6–10% of this population. The World Health Organization reports that approximately 1 in 10 women of reproductive age worldwide is affected by endometriosis [1–3]. Clinically, endometriosis is identified in roughly 25–50% of infertile women, while infertility develops in approximately 30–50% of women with endometriosis [4–6]. In laparoscopically assessed cohorts labeled as “unexplained infertility,” the prevalence has been reported to reach 40–45% [7]. The negative impact of endometriosis on fertility is multifactorial. The proposed mechanisms include a proinflammatory and prooxidative ovarian microenvironment, impaired oocyte competence, disrupted folliculogenesis, altered embryo developmental potential, and reduced endometrial receptivity [8–10]. In addition, peritoneal inflammation, adhesion formation, and tubal dysfunction may indirectly compromise fertilization and implantation [11]. Despite advances in in vitro fertilization (IVF), selecting an optimal treatment strategy for infertility in women with endometriosis remains clinically challenging. Surgical decision-making requires particular caution. Current evidence suggests that surgery for endometrioma may be associated with a decline in ovarian reserve and a reduction in anti-Müllerian hormone (AMH) levels [12]. At the same time, surgery does not consistently translate into improved IVF outcomes, and in selected patients, proceeding directly to IVF may be more rational and time-efficient [13, 14]. Therefore, the decision for surgery should be individualized, taking into account age, ovarian reserve, symptom burden, bilaterality, malignancy risk, and prior surgical history. This chapter aims to evaluate contemporary, evidence-based approaches to infertility management in women with endometriosis, with particular emphasis on improving IVF outcomes. Key areas include controlling inflammatory activity, optimizing oocyte quality, identifying and managing potential tubal pathology, and tailoring embryo transfer strategies to improve reproductive outcomes. 2. Factors contributing to infertility in endometriosis 2.1 Oocyte quality and the ovarian microenvironment Endometriosis – particularly when ovarian involvement is present – may adversely affect oocyte development by sustaining a chronic inflammatory milieu within the ovarian microenvironment. In the presence of an endometrioma, the follicular environment appears to demonstrate more pronounced inflammatory and oxidative stress features compared with unaffected ovarian tissue [9]. In endometriotic lesions, increased levels of proinflammatory cytokines – most notably interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α – have been reported, along with elevated reactive oxygen species (ROS). This inflammatory and oxidative environment may impair granulosa cell function, reduce mitochondrial membrane potential, and disrupt ATP production. Such cellular changes can compromise oocyte maturation, cytoplasmic competence, and fertilization capacity [8, 11]. Additionally, iron accumulation in ovarian tissue surrounding endometriomas – related to hemoglobin breakdown products – may amplify oxidative stress via free radical generation. Iron-mediated oxidative damage can further deteriorate the follicular milieu through lipid peroxidation and DNA injury [9]. Clinically, endometrioma has been associated with fewer oocytes retrieved during IVF cycles and, in some patient subsets, lower oocyte maturation rates. However, meta-analytic evidence suggests that implantation, clinical pregnancy, and live birth rates may remain comparable to those in the general infertile population in selected groups, even when an endometrioma is present [13]. Importantly, the effect of endometriosis on oocyte competence may depend more on disease severity than on the mere presence of the condition. Bilateral ovarian involvement, large endometriomas, and repeated ovarian surgery tend to exert a stronger impact on ovarian reserve and the follicular microenvironment [9, 13]. In contrast, women with a limited disease burden (e.g., unilateral small endometrioma and no prior surgery) may have IVF outcomes similar to those of the broader infertile population [13]. 2.2 Embryo development and genetic competence Compared with the evidence on oocyte competence, the effect of endometriosis on embryo development and genetic competence is more heterogeneous and remains debated. The available data report variable findings regarding fertilization rates, embryo developmental kinetics, and blastocyst formation in the context of endometriosis. These differences likely reflect disease stage, the presence and extent of ovarian involvement, and baseline ovarian reserve [9, 13]. In many IVF cohorts, fertilization and blastocyst development rates appear comparable to those in the general infertile population; however, some subgroups demonstrate a reduction in the number of embryos available. This reduction may be driven primarily by the lower number of retrieved oocytes and diminished ovarian reserve, rather than by a consistent decline in embryo quality per se [13]. From a mechanistic standpoint, the inflammatory and oxidative milieu associated with endometriosis may indirectly influence early embryo development via impaired oocyte cytoplasmic maturation and mitochondrial function. Elevated cytokine activity and oxidative stress can alter organelle function within the oocyte, resulting in variable effects on embryonic developmental potential [8, 11]. In a study evaluating oocyte cryopreservation outcomes, embryos generated after thawing from oocytes exposed to an endometrioma environment were associated with fewer high-quality day-3 embryos, higher fragmentation rates, and less favorable morphology compared with embryos derived from nonexposed oocytes [15]. With respect to embryo genetics, there is no strong evidence that endometriosis markedly increases aneuploidy rates. Meta-analytic data suggest that euploid embryo rates in women with endometriosis are broadly comparable to those observed in the general infertile population [10, 13]. Consequently, current practice does not consider endometriosis alone as an indication for preimplantation genetic testing. Instead, the decision for PGT-A (Preimplantation Genetic Testing for Aneuploidies) should be based on conventional clinical factors, such as maternal age, the number of embryos available, recurrent implantation failure, and recurrent pregnancy loss [6, 10]. 2.3 Endometrial receptivity and implantation Endometriosis is a complex inflammatory disorder that may compromise implantation not only through effects on embryo development but also via molecular alterations in endometrial receptivity. Changes in endometrial gene expression relevant to receptivity and an impaired progesterone response have been reported in women with endometriosis [3, 16]. Alterations in key receptivity-related markers – particularly HOXA10 (Homeobox A10), LIF (leukemia inhibitory factor), and integrin expression – have been implicated, potentially affecting implantation success. Disturbances in signaling pathways that regulate the window of implantation may interfere with trophoblast adhesion and downstream implantation processes [16]. Progesterone resistance is widely considered a central mechanism underlying implantation failure associated with endometriosis. Reduced progesterone receptor expression – particularly of the PR-B isoform – and disrupted progesterone response pathways may impair endometrial decidualization. These molecular changes have been linked to reduced implantation success [17]. In addition, activation of inflammatory signaling within the endometrium, altered steroid-response gene expression, and epigenetic dysregulation may contribute to the development and persistence of progesterone resistance [17]. While implantation rates may be reduced in advanced-stage disease, appropriate embryo selection and individualized transfer strategies can result in clinical pregnancy and live birth rates comparable to those of the broader infertile population in selected patient groups [10, 13]. 2.4 Endometriosis-associated hydrosalpinx: Tubal evaluation before IVF Hydrosalpinx is one of the most important tubal pathologies adversely affecting IVF success. Multiple clinical studies have demonstrated an association between hydrosalpinx and reduced implantation and pregnancy rates during IVF [18]. Reflux of hydrosalpinx fluid into the uterine cavity may impair implantation through both mechanical and toxic mechanisms, and the presence of hydrosalpinx has consistently been linked to lower implantation and pregnancy rates [18]. In women with endometriosis, tubal damage may develop as a result of chronic pelvic inflammation, peritubal adhesions, and distal tubal obstruction. The inflammatory and fibrotic processes associated with endometriosis can disrupt tubal function and may predispose them to hydrosalpinx formation [3, 11]. Tubal pathology may be more frequent in women with ovarian endometriomas, potentially reflecting the coexistence of pelvic adhesions and distal tubal damage [19]. Notably, tubal pathology may remain clinically silent in IVF patients with endometriomas and become apparent only after implantation failure. Therefore, tubal evaluation for hydrosalpinx before embryo transfer may be particularly relevant in women with ovarian endometriomas, especially those with otherwise unexplained implantation failure [19]. When hydrosalpinx is present, surgical management – typically salpingectomy or proximal tubal occlusion – remains a recommended preIVF strategy, supported by meta-analytic evidence demonstrating improved IVF pregnancy outcomes after treatment [20]. 3. Fertility treatment in endometriosis 3.1 Surgery versus IVF When defining a treatment strategy, preserving reproductive potential should be the central priority [6]. The decision for surgical management must be individualized. Although the contents of an endometrioma may exert potentially toxic effects on ovarian tissue, surgical excision can also lead to cortical tissue loss and vascular injury, resulting in an abrupt decline in ovarian reserve [9, 12, 15]. A significant reduction in AMH following laparoscopic endometrioma excision has been reported, with a more pronounced decline in bilateral disease and after repeat surgeries [12]. On the other hand, spontaneous conception may occur in the early months after surgery, and the first six months postoperatively are often considered the period with the highest likelihood of spontaneous pregnancy [14]. However, this benefit is highly dependent on patient selection and should not be generalized across all endometriosis phenotypes. Even when postoperative spontaneous conception is theoretically possible, failure to conceive within this window can complicate subsequent fertility management. Surgery-associated reduction in ovarian reserve may decrease oocyte yield if IVF becomes necessary, potentially reducing the probability of success [12, 21, 22]. The IVF outcomes in women with endometriomas suggest that proceeding without prior surgery is an acceptable approach for many patients [13, 22]. Therefore, in women with limited time to conception or diminished ovarian reserve, the potential time loss associated with waiting for spontaneous pregnancy after surgery should be carefully weighed [10, 21]. In practice, IVF is often favored in women with low or borderline ovarian reserve, prior ovarian surgery, advanced maternal age, or small endometriomas that do not interfere with oocyte retrieval; conversely, surgery may be indicated in the presence of suspected malignancy or severe pain symptoms [6]. At a molecular level, inflammation, cytokine activity, and progesterone resistance can influence implantation; however, robust evidence supporting that surgery fully normalizes these biological processes is lacking [11, 17]. Current clinical approaches and recommendations for endometriosis-associated infertility are summarized in Table 1. | Therapeutic approach | Mechanism of action | Evidence level | Clinical recommendation | |---|---|---|---| | Individualized ovarian stimulation | Optimizes follicular recruitment and oocyte yield | High | Recommended as standard approach | | Surgical treatment (endometrioma excision) | Removes inflammatory lesions and restores pelvic anatomy | Moderate | Recommended in selected patients | | Freeze-all strategy | Avoids impaired endometrial receptivity associated with a supraphysiological hormonal environment | Moderate | Recommended in selected cases | | GnRH agonist suppression | Reduces inflammatory activity and improves the implantation environment | Moderate | Selective use | | Tubal surgery (salpingectomy/proximal tubal occlusion) | Eliminates embryotoxic hydrosalpinx fluid and improves implantation potential | High | Recommended when hydrosalpinx is present | | Luteal phase support | Compensates for progesterone resistance and supports implantation | Moderate | Standard IVF practice | | Antiinflammatory diet and lifestyle optimization | Reduces systemic inflammation and oxidative stress; supports oocyte and endometrial function | Moderate | Recommended as a supportive strategy | | Antioxidant supplementation | Reduces oxidative stress and cellular damage | Low | Selective use; limited evidence | | Platelet-rich plasma (PRP) | Promotes tissue regeneration via growth factors and angiogenesis. | Low | Experimental | | Mesenchymal stem cell-based therapies | Immunomodulation and tissue repair | Low | Experimental | | Exosome-based therapies | Regulates intercellular signaling and regenerative pathways | Very low | Experimental/translational research | 3.2 Oocyte or embryo cryopreservation Protecting ovarian reserve is a key objective in fertility management for women with endometriosis. While endometriosis may affect the follicular microenvironment through chronic inflammation and oxidative stress [8], clinically meaningful declines in ovarian reserve are frequently related to surgical intervention [12]. Postoperative AMH reduction appears more pronounced in bilateral endometriomas, larger cysts, repeated surgeries, and scenarios associated with greater thermal damage to ovarian tissue. In older women, the clinical consequences of postoperative reserve loss may be more substantial [9, 12]. Accordingly, in women who desire future fertility, fertility preservation strategies – such as oocyte cryopreservation – should be considered, particularly before planned surgery [12]. 3.3 Ovarian stimulation and treatment strategies in endometriosis GnRH antagonist protocols are commonly preferred due to shorter stimulation duration, flexible trigger options, and improved management of OHSS risk. Importantly, antagonist protocols do not appear to confer a meaningful disadvantage in IVF outcomes compared with long agonist protocols. Long GnRH agonist protocols may be considered in selected endometriosis patients to suppress inflammatory activity; however, robust evidence supporting routine use for improved live birth rates is lacking [6, 23, 24]. 3.4 Selection and optimization of gonadotropins No consistent superiority has been demonstrated among gonadotropin preparations in women with endometriosis with regard to IVF outcomes. Recombinant FSH may offer dosing standardization. LH supplementation can be considered in selected scenarios – such as advanced age, diminished ovarian reserve, or prior suboptimal response – yet the evidence for improved pregnancy outcomes across all patient groups is inconsistent. Thus, gonadotropin selection should be individualized based on patient characteristics [6, 10, 21]. 3.5 Final oocyte maturation In antagonist cycles with a high OHSS risk, GnRH agonist trigger can be used safely. Dual-trigger approaches have been reported to improve oocyte maturation and embryo development in some subgroups; however, the effect appears to depend on patient selection, and evidence is insufficient to support routine use [6, 23, 24]. 3.6 Fresh versus freeze-all strategy As in other infertility populations, a freeze-all strategy may be preferred in cycles characterized by excessive follicular response, where a supraphysiologic hormonal milieu could compromise endometrial receptivity. In endometriosis populations, some meta-analyses suggest that frozen embryo transfer (FET)strategies may be associated with better pregnancy outcomes. Nevertheless, current evidence does not support routine freeze-all for all endometriosis patients. The transfer strategy should therefore be tailored on a case-by-case basis [10, 21, 25]. 3.7 GnRh agonist suppression before FET Although suppression of inflammatory activity has been associated with improved implantation rates in some reports, systematic reviews and meta-analyses have not demonstrated a clear improvement in live birth rates. Therefore, ultra-long GnRH agonist protocols may be better reserved for selected patients rather than used routinely [24, 26, 27]. 3.8 Medical suppression before IVF: Role of dienogest Dienogest may reduce symptoms and suppress inflammatory activity in infertile women with endometriosis; however, evidence that it consistently improves IVF outcomes is lacking [28]. In clinical practice, dienogest can be considered as a short-term pretreatment option in women with active pain symptoms, those not planning surgery, or when brief disease control is desired before IVF. Robust evidence does not support the routine long-term use of dienogest solely to improve IVF success [29]. 3.9 Luteal phase support in endometriosis Progesterone resistance and impaired endometrial receptivity have been described in endometriosis, which underscores the importance of adequate luteal support [16, 17]. However, since strong evidence does not support the routine use of high-dose or combined progesterone regimens in all patients, luteal phase support should be individualized [16, 17]. 3.10 Endometrial preparation and embryo transfer strategy in endometriosis In endometriosis, IVF outcomes appear to be influenced more by embryo quality, maternal age, and coexisting tubal factors than by the specific endometrial preparation protocol used for transfer [30]. 3.10.1 Natural-cycle FET versus hormone replacement therapy-frozen embryo transfer (HRT-FET) When comparing natural-cycle FET with hormone replacement therapy (HRT)-prepared FET cycles, no consistent superiority has been demonstrated regarding live birth rates. While natural cycles may offer a physiological luteal phase, HRT cycles are widely used due to scheduling flexibility and practical advantages. Therefore, cycle choice should be individualized based on ovulatory function and clinical logistics [30]. 3.10.2 Single embryo transfer Single embryo transfer in women with endometriosis can reduce the risk of multiple pregnancies while maintaining cumulative live birth rates. Endometriosis alone is not considered an indication for transferring multiple embryos [31]. 4. Lifestyle modification, nutrition, and oxidative stress control in endometriosis-related infertility The chronic inflammatory and oxidative stress environment characteristic of endometriosis may affect not only the pelvic microenvironment but also the systemic metabolic and inflammatory responses. Lifestyle, nutrition, and redox balance are, therefore, modifiable factors that may influence oocyte competence, embryo development, and ultimately, IVF outcomes [32]. Increased ROS can disrupt oocyte cytoplasmic maturation, mitochondrial function, and spindle stability. Elevated oxidative stress markers in follicular fluid have been reported in women with endometriosis, potentially impairing granulosa cell function and reducing oocyte competence [32]. Oxidative stress may also negatively influence early embryo development via DNA damage, lipid peroxidation, and mitochondrial dysfunction. From a nutritional perspective, antiinflammatory dietary patterns – particularly a Mediterranean-style diet – are often considered rational because of their potential to reduce systemic inflammation and oxidative burden. Diets with a balanced fatty acid profile, low glycemic load, and high antioxidant content have been associated with fertility-related outcomes [33]. Although a direct causal benefit on IVF endpoints has not been consistently demonstrated, favorable metabolic and inflammatory effects may provide indirect support. Sleep and circadian rhythm may also shape reproductive hormone regulation and oxidative balance. Melatonin is not only a sleep-regulating hormone but also a potent antioxidant that may influence the oocyte microenvironment. Sleep disturbances have been linked to increased inflammation and hormonal dysregulation, suggesting that optimized sleep may indirectly support fertility outcomes. However, there is no strong evidence that growth hormone secretion during sleep directly improves fertility or IVF outcomes [34]. Physiologically, nocturnal growth hormone secretion increases during sleep and can stimulate IGF-1 production; the IGF system is known to participate in ovarian steroidogenesis, granulosa cell proliferation, and follicular development, and may play a modulatory role in folliculogenesis and oocyte maturation. Antioxidant supplementation is theoretically appealing, as it could reduce oxidative stress and cellular injury. Nonetheless, Cochrane evidence does not support a clear improvement in live birth rates with antioxidant use in female infertility. Accordingly, supplementation may be considered selectively and in a targeted manner, rather than as a routine component of care [35]. Overall, lifestyle optimization is unlikely to be a stand-alone determinant of IVF success, but existing data suggest it may support reproductive potential by reducing inflammation, improving metabolic health, and mitigating oxidative stress. Thus, lifestyle optimization can be incorporated as a supportive strategy in the preIVF period for women with endometriosis. In clinical practice, supplements are frequently discussed with high expectations. Yet, current literature does not show that these agents reliably and directly increase IVF success. A more realistic perspective is to position them as supportive interventions aimed at reducing the chronic inflammatory and oxidative burden associated with endometriosis. Several molecules with antioxidant and antiinflammatory properties have been investigated. For instance, a randomized study of curcumin reported improvement in certain clinical parameters during assisted reproduction in women with endometriosis; however, the sample size was limited, and no clear superiority for live birth was demonstrated [36]. For vitamin D, the safest approach is replacement when deficiency is documented and avoidance of routine high-dose use. Antioxidants such as CoQ10 and N-acetylcysteine (NAC) may be considered for short-term in carefully selected patients (e.g., phenotypes suggestive of a high oxidative burden, prior poor response, substantial endometrioma load), with explicit counseling about the limited level of evidence. Omega-3 fatty acids have a plausible antiinflammatory rationale, but direct and consistent evidence for improved live birth in IVF populations with endometriosis remains limited. Polyphenols such as resveratrol may modulate endometriosis-related pathways through antiinflammatory mechanisms; thus, rather than promising a direct IVF benefit, it is more appropriate to frame them as experimental or theoretical supportive options [35, 37–39]. 5. Regenerative approaches in endometriosis-associated infertility Interest is growing in regenerative approaches that target the inflammatory microenvironment in endometriosis-associated infertility. Nevertheless, the current level of clinical evidence remains insufficient to support the routine incorporation of these therapies into standard IVF practice. Platelet-rich plasma (PRP). experimental and translational studies suggest that PRP may influence multiple biological pathways related to cellular proliferation, survival–apoptosis balance, intercellular signaling, and metabolic activity, potentially promoting regenerative processes at both ovarian and endometrial levels. At the endometrial level, intrauterine PRP has been reported – particularly in infertile patients with an inflammatory milieu, progesterone resistance, and impaired receptivity – to support endometrial proliferation and angiogenesis, with some studies suggesting improvements in endometrial thickness, implantation, and pregnancy rates. At the ovarian level, intraovarian PRP has been proposed as a potential regenerative strategy in settings characterized by inflammatory injury, diminished ovarian reserve, or an impaired follicular microenvironment, with hypothesized benefits for angiogenesis and tissue repair. However, in endometriosis-associated infertility, clinical data for both intrauterine and intraovarian PRP remain limited, and well-designed studies demonstrating clear effects on IVF outcomes and live birth rates are lacking. Therefore, PRP should still be considered experimental at present and – if used – should be restricted to carefully selected refractory cases with thorough and objective patient counseling [40–42]. Mesenchymal stem cell (MSC) and exosome-based approaches. MSC-derived exosomes have attracted attention as biologically active regulators with potential roles in endometriosis pathophysiology and treatment. Exosomes are small vesicles mediating intercellular communication and can carry proteins, lipids, and genetic material. They participate in immune regulation, proliferation, migration, and tissue remodeling. Endometriosis-related processes – such as inflammation, fibrosis, angiogenesis, and aberrant cellular proliferation – appear to be closely linked with exosome-mediated signaling pathways. Experimental studies suggest that MSC-derived exosomes may modulate inflammatory microenvironments, support tissue repair, and influence fibrotic pathways. However, clinical data regarding their impact on fertility outcomes – particularly IVF success – remain limited. Accordingly, MSC- and exosome-based interventions should be regarded as translational and investigational, pending stronger evidence on efficacy and safety before broader clinical adoption [43]. Immunomodulatory approaches (e.g., intralipid, IVIG, or targeted cytokine suppression strategies) have been explored in selected women with endometriosis and recurrent implantation failure. However, available studies are heterogeneous, and high-quality randomized evidence supporting routine use in endometriosis-related IVF populations is lacking. Such interventions may be considered only in carefully selected cases after alternative causes have been excluded [44]. In summary, regenerative and immunologic approaches are promising but remain experimental. For improving IVF outcomes in endometriosis-associated infertility, the cornerstone strategies continue to be careful patient selection, correction of tubal pathology, reduction of inflammatory burden where appropriate, and individualized stimulation and transfer protocols. Acknowledgments The author acknowledges the use of ChatGPT for language polishing and figure creation in the manuscript.

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