Ramazan Mercan
Can Benlioglu1- 1Department of Obstetrics and Gynecology, School of Medicine, Koc University, İstanbul, Türkiye
- 2Department of Obstetrics and Gynecology, American Hospital, İstanbul, Türkiye
Endometriosis and adenomyosis are prevalent causes of infertility, often coexisting in a significant proportion of patients. Although endometriosis typically does not negatively impact assisted reproductive technology (ART) outcomes, the presence of coexisting adenomyosis, mainly non-severe external forms, may slightly influence IVF/ICSI success rates. However, this impact is often minimal and may result in insignificant changes in statistical analyses. Recent studies underscore the critical role of accurate diagnostic techniques, such as ultrasound or MRI, in identifying severe adenomyosis characteristics, including diffuse involvement with junctional zone participation. This precise delineation is reassuring, as it is essential for tailoring assisted reproductive technology (ART) strategies to enhance success rates and reduce the confounding effects of adenomyosis, particularly when it coexists with endometriosis. Strategic approaches, such as ultralong GnRH agonist protocols or freeze-all strategies, may provide advantages in these scenarios. However, the need for extensive research is vital to understanding the complex interactions between endometriosis, adenomyosis, and ART outcomes. This ongoing exploration is particularly important in cases where coexisting adenomyosis might not significantly influence statistical results.
Introduction
Endometriosis and adenomyosis can cause infertility and often present together, with co-occurrence rates approaching 90%. This high coexistence rate underscores the complexity and necessitates further research (1). Both conditions share evolutionary theories and pathophysiological mechanisms, including Müllerian metaplasia, stem cell differentiation and genetic alterations, elevated inflammatory markers. Despite their shared characteristics, the published data about the impact of concurrent endometriosis and adenomyosis on assisted reproductive technology (ART) outcomes is limited.
We critically appraise the current literature, primarily focusing on meta-analyses and large cohort studies, to evaluate the impacts of adenomyosis and endometriosis on ART outcomes, particularly in cases where they occur concurrently. By scrutinizing the data, we aim to identify scientific pitfalls and challenges in the existing studies, emphasizing the high concordance rate between these two conditions and their potential impact on reported outcomes. Additionally, we explore various mitigation strategies, including surgery, optimal ovarian stimulation protocols, and frozen embryo transfer (FET) efficacy in affected patients.
Endometriosis
Definition, pathophysiology, prevalence, clinical manifestations and rationale behind the infertility
Endometriosis is defined by endometrial glands and stroma external to the uterus and impacts approximately 6%–8% of the general population and 20%–30% of women experiencing subfertility (1). Classification is typically based on the anatomical location of the lesions, including peritoneal, ovarian, or deep infiltrating endometriosis, with patients presenting multiple sites concurrently (2). Clinical manifestations include chronic pelvic pain, dysmenorrhea, dyspareunia, dyschezia, and infertility. While the precise etiology of endometriosis remains vague, several etiopathogenetic mechanisms have been hypothesized, including retrograde menstruation, Müllerian metaplasia, stem cell differentiation, lymphatic dissemination, and epigenetic modifications.
Endometriosis is highly prevalent among subfertilite population, but despite this correlation, the precise pathophysiological mechanisms underlying this association remain inconclusive, aside from tubal blockage resulting from adhesion formation. Several ideas have been proposed, including reduced oocyte quality, impaired endometrial receptivity, elevated levels of inflammatory markers, cytokines, and growth factors, overexpression of P450 enzymes, oxidative stress, prostaglandin imbalances, and the presence of coexisting conditions such as adenomyosis.
The ambiguous association between endometriosis and subfertility can also be seen in studies showing IVF/ICSI success rates of endometriosis patients. For example, in Horton et al.'s meta-analysis of 29 studies, the authors found a 15% reduction in conception likelihood and a 12% reduction in live birth rates (LBR) after IVF/ICSI in women with endometriosis compared to those without (3). However, these effects either lost their significance in subgroup analyses or, in the case of deep infiltrating endometriosis (DIE), the population could not be included due to increased heterogeneity among the studies. Moreover, Santully et al. claimed that endometrioma per se is not a cause of infertility, as the authors showed similar euploid blastocyst rates and outcomes after euploid embryo transfer in patients with and without endometriosis, indicating neither oocyte quality nor endometrial receptivity is impaired (2). Similar findings were also demonstrated in two recent large cohort studies (4, 5). Moreover, Qu et al.'s meta-analysis highlighted lower oocyte numbers and implantation rates in women with endometriosis but no difference in overall reproductive outcomes (6).
Overall, endometriosis might impact specific aspects of the IVF/ICSI process (like the number of oocytes retrieved and the rates of cycle cancellation); however, reproductive outcomes, including the success rates of euploid embryo transfers, are not significantly different from those observed in patients without endometriosis.
The impact of surgical treatment on IVF/ICSI outcomes
A meta-analysis by Hamdan et al. determined that IVF/ICSI outcomes are comparable between patients with and without endometrioma, with a higher cycle cancellation rate in the endometriosis group. Additionally, the authors concluded that surgical treatment does not alter outcomes in patients with endometrioma (7). Similarly, another meta-analysis conducted by Wu et al. found that surgical treatment of endometrioma prior to IVF has no significant effect on the number of mature oocytes or live birth rates. Nonetheless, the total number of oocytes retrieved was lower in the surgical treatment group (8). Consistent findings were reported in another Alshehre et al. meta-analysis, and they demonstrated a decrease in the number of oocytes and metaphase II (MII) oocytes in the surgical treatment group. Agreeing with the current literature, they found no significant differences in gonadotropin dose, duration of stimulation, total number of embryos, number of high-quality embryos, clinical pregnancy rates (CPR), implantation rates (IR), or live birth rates (LBR) (9).
Ultralong GnRH suppression and frozen embryo transfer (FET) in IVF/ICSI outcomes
A meta-analysis by Sallam et al. (10) indicated an increase in clinical pregnancy rates with ultralong GnRH agonist treatment. However, a more recent Cochrane review found no significant difference in outcomes between ultralong GnRH suppression and other treatment modalities (11).
The effectiveness of frozen embryo transfer (FET) in patients with endometriosis remains a topic of debate. Bourdon et al., in a retrospective study, observed higher cumulative pregnancy rates in patients with endometriosis undergoing FET compared to those undergoing fresh embryo transfer (12). Similarly, Wu et al., in a retrospective study involving 506 frozen and 255 fresh embryo transfers in patients with advanced endometriosis, reported better pregnancy and neonatal outcomes with FET than fresh embryo transfer (13). Conversely, Tan et al., in a retrospective cohort study, found no significant difference in early pregnancy outcomes between fresh and FET cycles in patients with endometriosis (14). In a recent meta-analysis, Paffoni et al. reported a modest decrease in live birth rates in patients with endometriosis. However, this difference was not statistically significant after adjusting for confounding factors (15).
Adenomyosis
Definition, pathophysiology, prevalence, clinical manifestations and rationale behind the infertility
Adenomyosis is the presence of endometrial glands and stroma within the myometrium of the uterus. Several pathophysiological mechanisms have been submitted, including invagination of the basal endometrium, Müllerian metaplasia, stem cell differentiation and epigenetic changes. It is also hypothesized that external adenomyosis may develop secondary to deep infiltrating endometriosis and is more frequent in patients with primary infertility and younger patients (16–18). In contrast, intrinsic adenomyosis could be associated with invasive interventions to the endometrium (like multiple curettages) and older age (19).
The prevalence of adenomyosis varies significantly based on age and diagnostic methods. Reports indicate a prevalence of 24.4% in women aged 40 and older and 7.52% in women younger than 40 (20, 21). Overall, prevalence ranges from 5% to 70% but generally stands around 10% for isolated adenomyosis, 1% for adenomyosis with coexisting fibroids, 6% for adenomyosis coexisting with endometriosis, and 7% for adenomyosis coexisting with both fibroids and endometriosis in women with subfertility (22). The increasing prevalence is attributed to advancements in ultrasound resolution and magnetic resonance imaging (MRI) for diagnosis (20). Classification of adenomyosis varies, often distinguishing between external and intrinsic types. Interestingly, symptoms do not significantly differ between these classifications (23).
Several theories have been proposed regarding the etiology of infertility in patients with adenomyosis, including increased uterotubal peristalsis affecting gamete transport and altered adhesion molecules (HOXA10, FOXO1A, leukemia inhibiting factor, integrin-beta-3 and osteopontin levels) (24, 25). Moreover, in a multicenter cohort study, transcriptomic analysis of the endometrium from patients with adenomyosis revealed a higher prevalence of a non-receptive endometrial profile compared to controls, suggesting that molecular changes in the endometrium may compromise endometrial receptivity (26). In a recent systemic review and meta-analysis, retrograde uterine contraction frequency was found to be increased in patients with endometriosis and adenomyosis, which may also contribute to menstrual pain and infertility (27)
Numerous published results on the impact of ART outcomes on patients with adenomyosis yield heterogeneous findings. Although the studies with euploid and donor cycles have shown similar pregnancy and live birth rates compared to those without adenomyosis (28, 29), several observational studies and meta-analyses demonstrated escalating trends in adverse ART outcomes. For instance, three meta-analyses showed lower clinical pregnancy and live birth rates and increased miscarriage rates in patients with adenomyosis (30–32). One of these studies, Nirgianakis et al., demonstrated a significant decrease in clinical pregnancy and live birth rates in patients with adenomyosis (33). However, the decrease in live birth rates became insignificant when adjusted for age, similar to euploid transfer and donor cycles mitigating female age's impact.
However, miscarriage rates present a different picture, with multiple studies having noted significantly higher miscarriage rates in patients with adenomyosis. This trend is particularly pronounced when adenomyosis is in the junctional zone (JZ), during donor oocyte cycles, and following euploid embryo transfers (34–36). Additionally, diffuse adenomyosis has been associated with decreased pregnancy rates and higher miscarriage rates, indicating a more adverse impact on reproductive outcomes in these cases (37).
In addition to the negative impact on ART outcomes, pregnancy complications are increased in patients with adenomyosis. Observational and meta-analysis have shown higher risks of preterm delivery, preterm premature rupture of membranes, and preeclampsia in patients with adenomyosis (38).
Ultralong GnRH suppression and frozen embryo transfer (FET) in IVF/ICSI outcomes
Ultralong GnRH agonist suppression in IVF/ICSI treatment aims to suppress the growth of ectopic endometrial tissue, decrease inflammatory markers, and reduce uterine size, theoretically improving treatment outcomes. The effectiveness of extended GnRH agonist suppression on IVF/ICSI outcomes remains controversial. For instance, two observational studies reported increased pregnancy rates following 1–3 months of GnRH agonist suppression (39, 40) and one retrospective study with 374 adenomyosis patients did not find a significant difference in IVF/ICSI outcomes with extended GnRH agonist suppression (41). In a study with propensity-score matching analysis, the authors found no significant difference in live birth or cumulative live birth rates between patients undergoing a GnRH-antagonist protocol with a freeze-all strategy and those using a long-acting GnRH agonist protocol in women with adenomyosis (42).
Coexisting endometriosis and adenomyosis
Coexistence of endometriosis with adenomyosis is prevalent, found in 65% to 90% of patients (43–45). Additionally, these pathologies share common pathophysiological features and similar genetic mutations like KRAS (46). Both conditions exhibit increased aromatase activity, leading to excessive estrogen production, up-regulation of inflammatory cytokines, and expression of cyclooxygenase-2, resulting in increased levels of prostaglandin-E2 and, ultimately, progesterone resistance (46).
There is limited data available on assisted reproductive technology (ART) outcomes in patients with coexisting endometriosis and adenomyosis. Two studies reported lower pregnancy rates in patients with coexistent endometriosis and adenomyosis compared to those with endometriosis alone (47, 48). Sharma et al. specifically noted significantly reduced pregnancy rates in patients with both conditions compared to those with endometriosis alone. However, there is no difference compared to patients with adenomyosis alone, suggesting that adenomyosis may primarily contribute to the decreased pregnancy rate (46). Another study by Shi et al., which included 176 patients with coexistent endometriosis and adenomyosis, revealed that patients who achieved live birth had smaller endometrioma and uterine sizes, indicating that anatomical distortion and diffuse adenomyosis might play a more critical role than adenomyosis alone (49).
Rees et al. (50) found that patients with coexisting endometriosis and adenomyosis had lower pregnancy rates compared to those with either endometriosis or adenomyosis alone. In a recent systematic review, Wang et al. reported that pregnancy rates were lower and miscarriage rates were higher in patients with adenomyosis, particularly in cases of diffuse adenomyosis, but not in asymptomatic cases (51). Additionally, coexistence with fibroids is more prevalent in internal adenomyosis than external forms, potentially resulting in lower pregnancy rates (18% vs. 2.8%) (52). It' s coherent with a recent study which demonstrated that patients with internal adenomyosis were typically older and more frequently had associated fibroids compared to those with external adenomyosis (53).
Kishi et al. reported that up to 96% of patients with adenomyosis in the outer myometrium had coexisting deep endometriosis (DE), contrasting with only 15% of those with inner myometrium adenomyosis (18).
Summary of findings
Endometriosis
Based on current findings, it is reasonable to conclude that in vitro fertilization (IVF) outcomes are not impaired in patients with endometriosis. Despite theoretical concerns about decreased endometrial receptivity and increased inflammatory markers, donor transfer cycles' data show similar pregnancy rates in those patients. Overall, studies indicate that surgical treatment before assisted reproductive technology (ART) does not improve outcomes. It can reduce ovarian reserve and the number of oocytes retrieved, potentially affecting cumulative live birth rates. While there are promising results for FET in patients with endometriosis, further studies are required to clarify its role. Some studies have reported improved pregnancy and neonatal outcomes with FET compared to fresh embryo transfer, while others have found no significant difference.
Adenomyosis
The overall evidence indicates that adenomyosis negatively impacts outcomes in assisted reproductive technology. While there are conflicting findings regarding pregnancy rates, patients with adenomyosis consistently exhibit higher miscarriage rates. Notably, IVF/ICSI outcomes do not differ significantly in patients with asymptomatic or focal adenomyosis compared to those without adenomyosis. However, diffuse adenomyosis and involvement of the junctional zone are associated with poorer outcomes in IVF/ICSI. For women with adenomyosis undergoing ART treatment, strategies such as a freeze-all approach or ultralong GnRH agonist protocols may be advantageous. Although progesterone resistance is acknowledged as a significant factor in infertility seen in patients with both endometriosis and adenomyosis, increasing progesterone doses for luteal support does not appear to enhance pregnancy rates, and there was no significant difference in progesterone levels between patients who achieved pregnancy and those who did not. These findings emphasize the multifactorial nature of infertility in adenomyosis and the need for comprehensive management strategies that consider both hormonal and anatomical aspects to optimize fertility outcomes in affected patients.
Adenomyosis as a confounding factor for infertile patients with endometriosis
These findings suggest that,
• Endometriosis typically involves external forms that do not significantly impact pregnancy and miscarriage rates.
• Patients with both endometriosis and severe or diffuse adenomyosis constitute a small subset of those with endometriosis, and even if they experience lower pregnancy rates within this group, their impact on overall results is minimal and does not change final statistical analysis.
• Patients with endometriosis coexisting with diffuse and severe adenomyosis that may impair ART outcomes are more likely prioritized as adenomyosis rather than endometriosis.
Conclusion
In conclusion, current findings indicate that IVF/ICSI outcomes do not differ between patients with endometriosis and those without. Although adenomyosis coexists in a majority of patients with endometriosis, it typically presents as external adenomyosis, which does not affect uterine anatomy and plays a minimal role in outcomes. The coexistence of endometriosis and internal adenomyosis is relatively rare. Although this subgroup exhibits lower live birth rates and higher miscarriage rates, its rarity often causes it to blend into broader endometriosis studies, preventing statistical significance in overall analyses unless a prospective study specifically focuses on these concurrent conditions.
Yet the sheer number of published studies for both pathologies, a skeptical approach is a must, considering the scarcity of concurrent studies and the fact that the published studies do not address these intertwined pathologies separately.
Data availability statement
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.
Author contributions
RM: Conceptualization, Investigation, Writing – original draft, Writing – review & editing. CB: Conceptualization, Writing – original draft, Writing – review & editing. GA: Writing – original draft, Writing – review & editing.
Funding
The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.
Acknowledgments
We acknowledge the use of ChatGPT 4.0, an artificial intelligence language model developed by OpenAI, for language improvement in this manuscript.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Generative AI statement
The author(s) declare that no Generative AI was used in the creation of this manuscript.
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
1. Practice Comitee of the American Society for Reproductive Medicine. Endometriosis and infertility. A comitee opinion. Fertil Steril. (2012) 98:591–8. doi: 10.1016/j.fertnstert.2012.05.031
2. Santulli P, Lamau MC, Marcellin L, Gayet V, Marzouk P, Borghese B, et al. Endometriosis-related infertility: ovarian endometrioma per se is not associated with presentation of infertility. Hum Reprod (Oxford England. (2016) 31:1765–75. doi: 10.1093/humrep/dew093
3. Horton J, Sterrenburg M, Lane S, Maheshwari A, Li TC, Cheong Y. Reproductive, obstetric, and perinatal outcomes of women with adenomyosis and endometriosis: a systematic review and meta-analysis. Hum Reprod Update. (2019) 25:593–633. doi: 10.1093/humupd/dmz012
4. Juneau C, Kraus E, Werner M, Franasiak J, Morin S, Patounakis G, et al. Patients with endometriosis have aneuploidy rates equivalent to their age-matched peers in the in vitro fertilization population. Fertil Steril. (2017) 108(2):284–8. doi: 10.1016/j.fertnstert.2017.05.038
5. Bishop LA, Gunn J, Jahandideh S, Devine K, DeCherney AH, Hill MJ. Endometriosis does not impact live-birth rates in frozen embryo transfers of euploid embryo transfer. Fertil Steril. (2020) 115(2):416–22. doi: 10.1016/j.fertnstert.2020.07.050
6. Qu H, Du Y, Yu Y, Wang M, Han T, Yan L. The effect of endometriosis on IVF/ICSI outcome: a systematic review and meta-analysis. J Obstet Gynecol Obstet Hum Reprod. (2022) 51(9):102446. doi: 10.1016/j.jogoh.2022.102446
7. Hamdan M, Dunselman G, Li TC, Cheong Y. The impact of endometrioma on IVF/ICSI outcomes: a systemic review and meta-analysis. Hum Reprod Update. (2015) 21(6):809–25. doi: 10.1093/humupd/dmv035
8. Wu CQ, Albert A, Alfaraj S, Taskin O, Alkusayer GM, Havelock J, et al. Live birth rate after surgical and expectant management of endometriomas after in vitro fertilization: a systemic review, meta-analysis, and critical appraisal of current guidelines and previous meta-analyses. J Minim Invasive Gynecol. (2019) 26(2):299–311.e3. doi: 10.1016/j.jmig.2018.08.029
9. Alshehre SM, Narice BF, Fenwick MA, Metwally M. The impact of endometrioma on in vitro fertilisation/intra-cytoplasmic injection IVF/ICSI reproductive outcomes: a systemic review and meta-analysis. Arch Gynecol Obstet. (2021) 303(1):3–16. doi: 10.1007/s00404-020-05796-9
10. Sallam HN, Garcia-Velasco JA, Dias S, Arici A, Abou-Setta A, Jaafar SH. Long-term pituitary down regulation before in vitro fertilization (IVF) for women with endometriosis. Cochrane Database Syst Rev. (2006) 2006(1):CD004635. doi: 10.1002/14651858.CD004635.pub2
11. Georgiou EX, Melo P, Sallam HN, Arici A, Garcia-Velasco JA, Abou-setta AM, et al. Long-term GNRH agonist therapy before in vitro fertilisation (IVF) for improving fertility outcomes in women with endometriosis. Cochrane Database Syst Rev. (2019) 2019(11):CD13240. doi: 10.1002/14651858.CDO13240.PUB2
12. Bourdon M, Santulli P, Maignien C, Gayet V, Pocate-Cheriet K, Marcellin L, et al. The deferred embryo transfer strategy improves cumulative pregnancy ratesz in endometriosis-related infertility: a retrospective matched cohort study. PLoS One. (2018) 13(4):e0194800. doi: 10.1371/journal.pone.0194800
13. Wu J, Yang X, Huang J, Yanping K, Wang Y. Fertility and neonatal outcomes of freeze- all vs. Fresh embryo transfer in women with advanced endometriosis. Front Endocrinol. (2019) 8(10):770. doi: 10.3389/fendo.2019.00770
14. Tan J, Cerillo M, Cruz M, Cecchino GN, Garcia-Velasco JA. Early pregnancy outcomes in fresh versus deffered embryo transfer cycles for endometriosis-associated infertility: a retrospective cohort study. J Clin Med. (2021) 10(2):344. doi: 10.3390/jcm10020344
15. Paffoni A, Casalechi M, De Ziegler D. Live birth after oocyte donation in vitro fertilization cycles in women with endometriosis. A systematic review and meta- analysis. JAMA Netw Open. (2024) 7(1):e2354249. doi: 10.1001/jamanetworkopen.2023.54249
16. Benagiano G, Habiba M, Brosens I. The pathophysiology of uterine adenomyosis: an update. Fertil Steril. (2012) 98:572–9. doi: 10.1016/j.fertnstert.2012.06.044
17. Leyendecker G, Bilgicyildirim A, Inacker M, Stalf T, Huppert P, Mall G, et al. Adenomyosis and endometriosis. Re-visiting their association and further insights into the mechanisms of auto-traumatisation. An MRI study. Arch Gynecol Obstet. (2015) 291:917–32. doi: 10.1007/s00404-014-3437-8
18. Kishi Y, Shimada K, Fujii T, Uchiyama T, Yoshimoto C, Konishi N, et al. Phenotypic characterization of adenomyosis occurring at the inner and outer myometrium. PLoS One. (2017) 12:e0189522. doi: 10.1371/journal.pone.0189522
19. Bourdon M, Santulli P, Oliveira J, Plu-Bureau G, Cormier J, Chapron C. Focal adenomyosis is associated with primary infertility. Fertil Steril. (2020) 114(6):1271–7. doi: 10.1016/j.fertnstert.2020.06.018
20. Puente JM, Fabris A, Patel J, Patel A, Cerillo M, Requena A, et al. Adenomyosis in infertile women: prevalence and the role of 3D ultrasound as a marker of severity of the disease. Reprod Biol Endocrinol. (2016) 14(1):60. doi: 10.1186/s12958-016-0185-6
21. Mishra I, Melo P, Easter C, Sephton V, Dhillon-Smith R, Coomarasamy A. Prevalence of adenomyosis in women with subfertility: systematic review and meta-analysis. Ultrasound Obstet Gynecol. (2023) 62:23–41. doi: 10.1002/uog.26159
22. Naftalin J, Nunes HN, Holland T, Mavrelos D, Jurkovic D. Association between ultrasound features of adenomyosis and severity of menstrual pain. Ultrasound Obstet Gynecol. (2015) 47(6):779–83. doi: 10.1002/uog.15798
23. Exacoustos C, Morosetti G, Conway F, Camilli S, Martire FG, Lazzeri L, et al. New sonographic classification of adenomyosis: do type and degree of adenomyosis correlate to severity of symptoms? J Minim Invasive Gynecol. (2020) 27:1308–15. doi: 10.1016/j.jmig.2019.09.788
24. Carrarelli P, Yen CF, Funghi L, Arcuri F, Tosti C, Bifulco G, et al. Expression of inflammatory and neurogenic mediators in adenomyosis. Reprod Sci. (2017) 24:369–75. doi: 10.1177/1933719116657192
25. Tremellen KP, Russell P. The distribution of immune cells and macrophages in the endometrium of women with recurrent reproductive failure. II: adenomyosis and macrophages. J Reprod Immunol. (2012) 93:58–63. doi: 10.1016/j.jri.2011.12.001
26. Juarez-Barber E, Cozzolino M, Corachan A, Pellicer N, Pellicer A, Ferrero H. Adjustment of progesterone administration after endometrial transcriptomic analysis does not improve reproductive outcome in women with adenomyosis. Reprod Biomed Online. (2023) 46(1):99–106. doi: 10.1016/j.rbmo.2022.09.007
27. Salmeri N, Di Stefano G, Vigano P, Stratton P, Somigliana E, Vercellini P. Functional determinants of uterine contractility in endometriosis and adenomyosis: a systematic review and meta-analysis. Fertil Steril. (2024) 122(6):1063–78. doi: 10.1016/j.fertnstert.2024.07.026
28. Nael S, Morin S, Werner M, Gueye N-A, Pirtea P, Patounakis G, et al. Three-dimension ultrasound diagnosis of adenomyosis is not associated with adverse pregnancy outcome following single thawed euploid blastocyst transfer: prospective cohort study. Ultrasound Obstet Gynecol. (2020) 56(4):611–7. doi: 10.1002/uog.22065
29. Benaglia L, Cardellicchio L, Leonardi M, Faulisi S, Vercellini P, Paffoni A, et al. Asymptomatic adenomyosis and embryo implantation in IVF cycles. Reprod Biomed Online. (2014) 29:606–11. doi: 10.1016/j.rbmo.2014.07.021
30. Younes G, Tulandi T. Effects of adenomyosis on in vitro fertilization treatment outcomes: a meta-analysis. Fertil Steril. (2017) 108:483–490.e3. doi: 10.1016/j.fertnstert.2017.06.025
31. Vercellini P, Consonni D, Dridi D, Bracco B, Frattaruolo MP, Somigliana E. Uterine adenomyosis and in vitro fertilization outcome: a systematic review and meta- analysis. Hum Reprod. (2014) 29:964–77. doi: 10.1093/humrep/deu041
32. Cozzolino M, Tartaglia S, Pellegrini L, Troiano G, Rizzo G, Petraglia F. The effect of adenomyosis on IVF outcomes. A systemic review and meta-analysis. Rep Sci. (2022) 29:3177–93. doi: 10.1007/s43032-021-00818-6
33. Nirgianakis K, Kalaitzopoulos DR, Schwartz ASK, Spaanderman M, Kramer BW, Mueller MD, et al. Fertility, pregnancy and neonatal outcomes of patients with adenomyosis: a systematic review and meta-analysis. Reprod Biomed Online. (2021) 42:185–206. doi: 10.1016/j.rbmo.2020.09.023
34. Cozzolino M, Cosentino M, Loiudice L, Galliano D, Pellicer A, Exacoustos C. Impact of adenomyosis on in vitro fertilization outcomes in women undergoing donor oocyte transfers: a prospective observational study. Fertil Steril. (2024) 121(3):480–8. doi: 10.1016/j.fertnstert.2023.11.034
35. Martinez-Conejero JA, Morgan M, Montesinos M, Fortuno S, Meseguer M, Simon C, et al. Adenomyosis does not affect implantation, but is associated with miscarriage in patients undergoing oocyte donation. Fertil Steril. (2011) 96:943–50. doi: 10.1016/j.fertnstert.2011.07.1088
36. Stanekova V, Woodman RJ, Tremellen K. The rate of euploid miscarriage is increased in the setting of adenomyosis. Hum Reprod Open. (2018) 2018:hoy011. doi: 10.1093/hropen/hoy011
37. Huang Y, Zhao X, Chen Y, Wang J, Zheng W, Cao L. Miscarriage on endometriosis and adenomyosis in women by assisted reproductive technology or with spontaneous conception: a systematic review and meta-analysis. Biomed Res Int. (2020) 2020:4381346. doi: 10.1155/2020/4381346
38. Maheshwari A, Gurunath S, Fatima F, Bhattacharya S. Adenomyosis and subfertility: a systematic review of prevalence, diagnosis, treatment and fertility outcomes. Human Reprod Update. (2012) 18:374–92. doi: 10.1093/humupd/dms006
39. Niu Z, Chen Q, Sun Y, Feng Y. Long-term pituitary downregulation before frozen embryo transfer could improve pregnancy outcomes in women with adenomyosis. Gynecol Endocrinol. (2013) 29:1026–30. doi: 10.3109/09513590.2013.824960
40. Park CW, Choi MH, Yang KM, Song IO. Pregnancy rate in women with adenomyosis undergoing fresh or frozen embryo transfer cycles following gonadotropin-releasing hormone agonist treatment. Clin Exp Reprod Med. (2016) 43:169–73. doi: 10.5653/cerm.2016.43.3.169
41. Chen M, Luo L, Wang Q, Gao J, Chen Y, Zhang Y, et al. Impact of gonadotropin- releasing hormone agonist Pre-treatment on the cumulative live birth rate in infertile women with adenomyosis treated with IVF/ICSI: a retrospective cohort study. Front Endocrinol (Lausanne). (2020) 11:318. doi: 10.3389/fendo.2020.00318
42. Zhang L, Cai H, Liu X, Xiong Y, Liang X, Shi J. Comparison of pregnancy outcomes between GnRH antagonist protocol with freeze-all strategy and long-acting GnRH agonist protocol in women with adenomyosis undergoing IVF/ICSI: a propensity- score matching analysis. BMC Pregnancy Childbirth. (2022) 22(1):946. doi: 10.1186/s12884-022-05276-9
43. Aleksandrovych V, Basta P, Gil K. Current facts constituting an understanding of the nature of adenomyosis. Adv Clin Exp Med. (2019) 28:839–46. doi: 10.17219/acem/79176
44. Kunz G, Beil D, Huppert P, Noe M, Kissler S, Leyendecker G. Adenomyosis in endometriosis prevalence and impact on fertility. Evidence from magnetic resonance imaging. Hum Reprod. (2005) 20:2309–16. doi: 10.1093/humrep/dei021
45. Sunkara SK, Khan KS. Adenomyosis and female fertility: a critical review of the evidence. J Obstet Gynaecol. (2012) 32:113–6. doi: 10.3109/01443615.2011.624208
46. Bulun S, Yildiz S, Adli M, Tsai S, Wei JJ, Yin P. Endometriosis and adenomyosis: shared pathophysiology. Fertil Steril. (2023) 119(5):746–50. doi: 10.1016/j.fertnstert.2023.03.006
47. Sharma S, Bathwal S, Agarwal N, Chattopadhyay R, Saha I, Chakravarty B. Does presence of adenomyosis affect reproductive outcome in IVF cycles? A retrospective analysis of 973 patients. Reprod Biomed Online. (2019) 38:13–21. doi: 10.1016/j.rbmo.2018.09.014
48. Ballester M, Roman H, Mathieu E, Touleimat S, Belghiti J, Daraï E. Prior colorectal surgery for endometriosis-associated infertility improves ICSI-IVF outcomes: results from two expert centres. Eur J Obstet Gynecol Reprod Biol. (2017) 209:95–9. doi: 10.1016/j.ejogrb.2016.02.020
49. Shi J, Zhang J, Li X, Jia S, Leng J. Pregnancy outcomes in women with infertility and coexisting endometriosis and adenomyosis after laparoscopic surgery: a long-term retrospective follow-up study. BMC Prenancy Health. (2021) 128:383. doi: 10.1186/s12884-021-03851-0
50. Rees CO, Rupert IAM, Nederend J, Mischi M, van Vliet HAAM, Schoot BC. Women with combined adenomyosis and endometriosis on MRI have worse IVF/ICSI outcomes compared to adenomyosis and endometriosis alone: a matched retrospective cohort study. Eur J Obstet and Gynecol. (2022) 271:223–34. doi: 10.1016/j.ejogrb.2022.02.026
51. Wang X-L, Xu Z-W, Huang Y-Y, Lin S, Lyu G-R. Different subtypes of ultrasound- diagnosed adenomyosis and in vitro fertilization outcomes: a systematic review and meta-analysis. Acta Obstet Gynecol Scand. (2023) 102(6):657–68. doi: 10.1111/aogs.14580
52. Bourdon M, Oliveira J, Marcellin L, Santulli P, Bordonne C, Maitrot Mantelet L, et al. Adenomyosis of the inner and outer myometrium are associated with different clinical profiles. Hum Reprod. (2021) 36:349–57. doi: 10.1093/humrep/deaa307
Keywords: endometriosis, in vitro fertilization, coexisting endometriosis and adenomyosis, Ultralong GnRH suppression, frozen embryo transfer
Citation: Mercan R, Benlioglu C and Aksakal GE (2024) Critical appraisal and narrative review of the literature in IVF/ICSI patients with adenomyosis and endometriosis. Front. Reprod. Health 6:1525705. doi: 10.3389/frph.2024.1525705
Received: 10 November 2024; Accepted: 11 December 2024;
Published: 24 December 2024.
Edited by:
Shevach Friedler, Barzilai Medical Center, IsraelReviewed by:
Noemi Salmeri, San Raffaele Scientific Institute (IRCCS), ItalyCopyright: © 2024 Mercan, Benlioglu and Aksakal. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Ramazan Mercan, cm1lcmNhbkBnbWFpbC5jb20=