Abstract
Purpose
Adenomyosis is a poorly understood entity with no unified treatment protocol. It has been thought to only affect the quality of life of older women, but growing evidence is highlighting the increased frequency of adenomyosis in younger patients and its possible effects on fertility outcomes. This can have a great impact on how clinicians screen, diagnose, and treat this condition. The aim of this review is to explore the relationship between adenomyosis and infertility.
Methods
A literature search of the keywords “adenomyosis”, “infertility”, “pregnancy” and “fertility” was conducted using the PubMed and Medline search engines. The articles selected were observational, systematic reviews, meta-analyses, and randomized controlled trials. The search was limited to English, abstracts were screened, and articles were selected.
Results
The literature reports lower clinical pregnancy rates, lower live birth rates, higher miscarriage rates, and higher odds of adverse obstetric outcomes in patients with adenomyosis. Treatment seems to be associated with higher pregnancy rates and live births rates.
Conclusion
An association between adenomyosis and infertility seems to exist, and treatment could lead to improved fertility outcomes.
Keywords: Adenomyosis, Infertility, Pregnancy, Fertility
Introduction
Adenomyosis has been vaguely described as a benign condition of endometrial invasion into the myometrium leading to an enlarged uterus and symptoms of abnormal uterine bleeding [1]. The exact pathogenesis of adenomyosis has not been established, but some theories have been widely accepted and adopted by physicians. The most common theory suggests that adenomyosis results from the invagination of the endometrial basalis into the myometrium [2]. Another possible theory is that adenomyotic lesions are due to metaplasia of displaced Mullerian remnants or differentiation of adult stem cells [2]. Both of these theories can explain how parity may be a risk factor for the development of adenomyosis. Pregnancy could facilitate the extension of the endometrial lining into the myometrium due to the invasive nature of the trophoblast [3]. Pregnancy can also create a highly estrogenic milieu in which ectopic endometrial foci may develop [4]. Furthermore, multiparous women are more likely to undergo a hysterectomy for any symptomatic condition, and so for a long time, adenomyosis was thought to be linked to multiparity and was only identified on histopathology in women undergoing hysterectomies [5, 6]. Diagnostic techniques have developed to become less invasive over the years. Hysterosalpingography (HSG) was the first imaging modality used to diagnose adenomyosis. Adenomyosis on HSG may appear as small diverticula extending into the myometrium in about 25% of patients [1]. On addition of contrast, a honeycomb appearance may be noted as contrast accumulates in those sacs [1]. However, due to its low sensitivity, HSG is not commonly used to diagnose adenomyosis. Magnetic resonance imaging (MRI) has been reported to have a sensitivity ranging from 46.1% to 90% in detecting adenomyosis [2]. On MRI, the most important finding in diagnosing adenomyosis is thickness of the junctional zone exceeding 12 mm [] [3]. Its principal limitation, however, is absence of a definable junctional zone in about 20% of premenopausal women [3]. It has been implicated that the transvaginal ultrasound (TVUS) may have a similar sensitivity (89%) as the MRI [7, 8]. On transvaginal ultrasound (TVUS), these features include asymmetrical myometrial thickening, linear striations, myometrial cysts, hyperechoic islands, irregular endometrial-myometrial junction, parallel shadowing and localized adenomyomas [4, 5]. Nowadays, with the widespread use of in-clinic TVUS and with women delaying their first pregnancy, adenomyosis is being diagnosed more frequently in younger patients [5]. However, because there is no uniform consensus on the diagnostic criteria for adenomyosis among societies, the potential for bias in studies remains high [6].
Adenomyosis commonly occurs with other comorbidities such as leiomyomas and endometriosis which can make it difficult to attribute patients’ symptoms to the adenomyotic process itself [4]. Clinical presentations that commonly accompany the diagnosis are abnormal uterine bleeding manifesting as heavy, irregular or intermenstrual bleeding, dysmenorrhea, pelvic pain, and dyspareunia [9]. Furthermore, patients presenting with infertility are being diagnosed with adenomyosis at increasing frequencies, suggesting that the condition may be linked to subfertility or infertility [10]. It has been proposed that a number of implantation markers are aberrantly expressed in patients with endometriosis, contributing to low implantation rates and infertility [7]. This hypothesis can also be extended to adenomyosis. Altered endometrial function and receptivity leading to a proinflammatory environment and high oxidative stress may impair implantation and survival of embryos [8]. Other proposed mechanisms of infertility in patients with adenomyosis are related to abnormal utero tubal transport. Intrauterine abnormalities, such as adenomyomas, may obstruct the tubes and distort the uterine cavity, reducing implantation rates. Destruction of normal myometrial architecture and function may also lead to disturbed uterine peristalsis and affect sperm transport [8]. The prevalence of adenomyosis in infertile women has been reported to be around 24.4% in women aged 40 years and above, and around 7.5–22% in women aged less than 40 [11, 12]. These numbers are alarming and highlight the need to further understand the relationship between adenomyosis and fertility outcomes. In this review, we explore the evidence regarding the impact of adenomyosis on infertility, as well as review the adverse obstetric outcomes of adenomyosis, and the effect of treatment on fertility outcomes.
Methods
To review the topic of the impact of adenomyosis on infertility, a literature search was performed using PubMed and Medline databases. The search words used were “adenomyosis”, “infertility”, “pregnancy” and “fertility”. Boolean operators were used to combine the search words as follows: Adenomyosis AND (Infertility OR pregnancy OR fertility). The search limits were English language, publication date starting 2000 till present and articles type including systematic reviews, meta-analyses, randomized controlled trials and observational studies. Abstracts were screened, duplicates were removed, and relevant articles were selected. We included articles that were specific to adenomyosis and those that reported outcomes in terms of pregnancy rates, miscarriage rates and odds of adverse obstetric outcomes. We also looked into papers that highlighted the effect of treatment on fertility outcomes. Papers were mostly meta-analyses and systematic reviews. We excluded abstracts, letters and articles that were analyzed in the meta-analyses.
Results
Impact of adenomyosis on infertility
Studies addressing the effect of adenomyosis on infertility reported outcomes in terms of clinical pregnancy rates and miscarriage rates after assisted reproductive technology (ART). In a meta-analyses by Vercellini et al. of 1865 patients, women with adenomyosis had a 28% reduction in the likelihood of clinical pregnancy with ART compared to women without adenomyosis [13]. Their results showed that the clinical pregnancy rate in women with adenomyosis was 40.5% compared to 49.8% in women without the condition [13]. Their analysis yielded a pooled risk ratio of 0.72 (95% CI, 0.55–0.95) [13]. Lower clinical pregnancy rates in patients with adenomyosis have also been reported by Younes et al. in a meta-analysis of 11 studies with 519 patients, with a statistically significant combined odds ratios of 0.73 per cycle and 0.75 per embryo [14]. Younes et al. also reported a 41% decrease in live pregnancy rates in patients with adenomyosis [14].
Similarly, in a prospective multicenter study by Mavrelos et al. in which 375 patients presenting with infertility were screened with an ultrasound, 19.2% of patients were diagnosed with adenomyosis, of which 40% achieved clinical pregnancy [15]. Of these, 78.7% of clinical pregnancies resulted in live births. The authors also found that patients with adenomyotic features were significantly less likely to have a clinical pregnancy following embryo transfer versus those without the condition (29.2%, CI 18.6–39.6 versus 42.6%, CI 0.47–1, respectively) [15]. A logistic regression was also performed with clinical pregnancy as dependent variable and age, anti-mullerian hormone (AMH), antral follicular count (AFC), body mass index (BMI) and presence of adenomyosis as independent variables. They found AFC (odds ratio 1.07, CI 1.03–1.1) and accumulation of four or more features of adenomyosis as a significant predictor of clinical pregnancy (odds ratio 0.35, CI 0.15–0.82) [15]. Furthermore, Mavrelos et al. calculated the probability of clinical pregnancy at each adenomyosis level which consistently decreased from 42.7% (CI 37.1–48.3) in patients with adenomyosis score of zero to 13% in patients with a score of 7 (2.2–23.9) [15].
In a meta-analysis of 17 observational studies, Nirgianakis et al. calculated the odds ratio of clinical pregnancy rate in 4 separate subgroups divided according to the ART protocols received and then reported a pooled odds ratio showing a statistically significant decrease in live pregnancy rates in patients with adenomyosis compared to those without (OR 0.69, CI 0.51–0.94) in the crude analysis, but became close to insignificant upon adjusted analysis for age (OR 0.78, CI 0.58–1.05) and with matching to endometriosis (OR 0.66, CI 0.39–1.12) [16]. Live birth rates were consistently not significantly different in the crude analysis (OR 0.58, CI 0.21–1.17) and age-adjusted analysis (OR 0.75, CI 0.35–1.58) [16]. Nirgianakis et al. further reported a significantly higher miscarriage rate in patients with adenomyosis in the crude analysis (OR 2.17, CI 1.24–3.8) and age-adjusted analysis (OR 2.5, CI 1.26–4.95), but not when matched to an endometriosis group (OR 1.82, CI 0.3–11.16) [16].
The reproducibility of decreased clinical pregnancy rates across these studies highlights the established association between adenomyosis and infertility.
Miscarriage rates were consistently increased across the literature in patients with adenomyosis. Vercellini et al. reported a miscarriage rate of 31.9% in patients with adenomyosis, compared to 14.1% in patients without the condition (RR 2.12, CI 1.2–3.75) [13]. Younes et al. similarly reported an odds ratio of 2.2 (CI 1.53–3.15) [14]. In two systematic reviews and meta-analyses by Horton et al. and Huang et al., an increased risk of miscarriage was noted in patients with adenomyosis (OR 3.4, CI 1.41–8.65 and OR 2.81, CI 1.44–5.47, respectively) [17, 18]. Mavrelos et al. reported no statistically significant difference in miscarriage rates between patients with adenomyosis versus patients without (RR 0.29, CI 0.04–2) [15]. These results are likely due to the much smaller number of patients with adenomyosis (21 patients) compared to the control group that included 129 patients [15].
Pregnancy and obstetric outcomes
In addition to its consequences on pregnancy rates and miscarriages, adenomyosis has also been associated with adverse obstetric outcomes. In a systematic review by Maheshwari et al., one study was identified that reported an increased risk of preterm delivery (OR 1.84, CI 1.32–4.31) and preterm premature rupture of membrane (OR 1.98, CI 1.39–3.15) in women with adenomyosis [10]. They also described reports of uterine rupture or perforation, uterine atony and hemorrhage, ectopic pregnancy, and rapid enlargement in adenomyosis after controlled ovarian hyperstimulation [10]. In a meta-analysis that included 2,517,516 patients, Bruun et al. assessed obstetric outcomes in adenomyosis and found higher odds of preterm delivery (OR 3.09, CI 1.88–5.09), and a higher risk of small for gestational age infants (OR 3.23, CI 1.71–6.09) in patients with adenomyosis [19]. Razavi et al. similarly reported an increased likelihood of preterm birth (OR 3.05, CI 2.08–4.47), small for gestational age infants (OR 3.22, CI 1.71–6.08), in addition to higher rates of pre-eclampsia (OR 4.35, CI 1.07–17.72) in women with adenomyosis [20].
Nirgianakis et al. provided a more detailed analysis of pregnancy, obstetric and neonatal outcomes. They reported pooled odds ratios and they adjusted the results for age. Nirgianakis et al. found higher odds of preterm delivery (OR 2.83, CI 2.18–3.54) and pre-eclampsia (OR 4.32, CI 1.68–11.09) in patients with adenomyosis but no difference in severe preterm delivery (OR 2.2, CI 0.82–5.89) [16]. Their meta-analysis showed significantly higher risks of caesarean section in patients with adenomyosis (OR 2.48, CI 1.44–4.26), even after adjustment and sensitivity analysis (OR 4.44, CI 2.64–7.46), and higher odds of fetal malpresentation in this population (OR 3.05, CI 1.7–5.81) [16]. Post-partum hemorrhage was also significantly increased (OR 2.9, CI 1.39–6.05) [16]. In their analysis of neonatal outcomes, the authors found a significant increase in small for gestational age infants (OR 2.86, CI 1.68–4.88) and birthweight less than 2500 g (OR 2.82, CI 1.2–6.62), but no difference in birthweight less than 1500 g (OR 5.67, CI 0.91–35.34) in infants born to mothers with adenomyosis. Furthermore, they reported no difference in odds of intrauterine fetal death (OR 1.43, CI 0.34–6.04), or in APGAR scores less than 7 (OR 1.63, CI 0.56–4.7) [16].
Effect of treatment on fertility
There are no current international guidelines to follow for surgical or medical treatment of adenomyosis [21]. Regardless of the modality, treatment of adenomyosis seems to positively affect fertility outcomes. Pregnancy and live birth rates in adenomyosis have consistently been reported to improve after treatment. Maheshwari et al. reported improvement in pregnancy rates after treatments with danazol-loaded devices (combined pregnancy rate 41% after insertion and removal of device), gonadotropin releasing hormone agonist (GnRH) therapy (spontaneous pregnancy achieved), conservative surgery (live birth rate 36.2%), and uterine artery embolization (live birth rate 83.3% at 35 months following treatment) [10]. In their systematic review, Grimbizis et al. also reported pregnancy rates of 60.5% after complete excision, 46.9% after partial excision of adenomyosis, and 55.6% after non-excisional techniques [22]. The odds ratio of clinical pregnancy rates after surgery for adenomyosis was 6.22 (CI 2.34–16.54) in a meta-analysis by Younes et al. [14]. They also noted that treatment with GnRH agonists prior to IVF in women with adenomyosis seemed to be beneficial [14]. In another review, Younes et al. reported conception after conservative surgery with or without adjuvant medical treatment in three-fourths of the patients treated for adenomyosis [23].
In a systematic review on current treatment options, Rocha et al. reported a pooled pregnancy rate of 40.7% when using GnRH analogues for 24 weeks after surgery [24]. They also noted that a long stimulation protocol had better outcomes compared to a short stimulation protocol in pregnancy rate (43.3% vs 31.8%, P = 0.0001), live birth (43% vs 23.1%, P = 0.005), and miscarriage (18.5% vs 31.1%, P < 0.0001) [24]. Tan et al. also compared reproductive outcomes following surgical or surgical and medical management in diffuse versus focal adenomyosis. Reproductive outcome rates seemed to be higher after treatment of patients with focal adenomyosis than those with diffuse adenomyosis. After surgery alone, pregnancy rates were 49.1% in the focal adenomyosis group versus 38.5% in the group with diffuse adenomyosis, and successful delivery rates were 38.6% versus 31.3% in the focal and diffuse groups respectively; however, the miscarriage rates were surprisingly higher in the focal adenomyosis group than the diffuse cohort (27.6% versus 16.2%) [25]. When both surgical and medical treatments were combined, pregnancy rates increased to 67.1% in patients with adenomyosis and dropped to 17.6% in patients with diffuse adenomyosis, successful delivery rates reached 61.3% and 9.8%, respectively, and miscarriage rates were higher in the group with diffuse adenomyosis (33.3% in diffuse vs 11.6% in focal) [25]. Their combined results showed a pregnancy rate of 31.3%, successful delivery rate of 23.8%, and miscarriage rate of 19.6% after any treatment in patients with diffuse adenomyosis compared to pregnancy rates of 54.8%, successful delivery rates of 45.1%, and miscarriage rates of 21.8% after any treatment in patients with focal adenomyosis [25].
Most recently, Xie et al. conducted a prospective observational study in which 45 patients with adenomyosis were treated with GnRH therapy and followed up for 6 months [26]. Various outcomes were reported, one of which was an increase in the mean elasticity score which was shown to be directly associated with spontaneous pregnancy in infertile patients. In this study, 12 patients achieved pregnancy at the 6-month follow-up and were found to have a significantly higher elasticity score (3.6 compared to 2.3 before therapy, P = 0.004) after GnRH agonist treatment, while the other 33 patients who did not achieve pregnancy were found to have no statistically significant difference in the elasticity score (2.2 vs 2.5 before treatment, P = 0.77) [26].
Conclusion
Adenomyosis has been regarded as a disease of the multiparous until recently when speculations arose on the possibility of this condition being associated with infertility. The evidence so far has favored this hypothesis, and adenomyosis seems to be indeed associated with decreased pregnancy rates, lower rates of live births, higher miscarriage rates, and adverse obstetric, pregnancy and neonatal outcomes. Both medical and surgical treatments of adenomyosis seem to have a positive effect on fertility outcomes leading to improved pregnancy and live birth rates. It is important to note, however, that pregnancy rates may be biased and are not enough to be solely used as an objective measure of infertility. More evidence is needed to establish a definite association between adenomyosis and infertility, and design a standardized protocol for the treatment of adenomyosis when fertility is desired.
Author contributions
All authors contributed equally to this review paper.
Declarations
Conflict of interest
The authors have no relevant financial or non-financial interests to disclose.
Footnotes
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- 1.Bird CC, McElin TW, Manalo-Estrella P. The elusive adenomyosis of the uterus–revisited. Am J Obstet Gynecol. 1972;112(5):583–593. doi: 10.1016/0002-9378(72)90781-8. [DOI] [PubMed] [Google Scholar]
- 2.García-Solares J, et al. Pathogenesis of uterine adenomyosis: invagination or metaplasia? Fertil Steril. 2018;109(3):371–379. doi: 10.1016/j.fertnstert.2017.12.030. [DOI] [PubMed] [Google Scholar]
- 3.Weiss G, et al. Adenomyosis a variant, not a disease? Evidence from hysterectomized menopausal women in the Study of Women's Health Across the Nation (SWAN) Fertil Steril. 2009;91(1):201–206. doi: 10.1016/j.fertnstert.2007.11.025. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Vercellini P, et al. Adenomyosis: epidemiological factors. Best Pract Res Clin Obstet Gynaecol. 2006;20(4):465–477. doi: 10.1016/j.bpobgyn.2006.01.017. [DOI] [PubMed] [Google Scholar]
- 5.Harada T, et al. The Impact of Adenomyosis on Women's Fertility. Obstet Gynecol Surv. 2016;71(9):557–568. doi: 10.1097/OGX.0000000000000346. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Taran FA, et al. Clinical characteristics indicating adenomyosis at the time of hysterectomy: a retrospective study in 291 patients. Arch Gynecol Obstet. 2012;285(6):1571–1576. doi: 10.1007/s00404-011-2180-7. [DOI] [PubMed] [Google Scholar]
- 7.Reinhold C, et al. Diffuse adenomyosis: comparison of endovaginal US and MR imaging with histopathologic correlation. Radiology. 1996;199(1):151–158. doi: 10.1148/radiology.199.1.8633139. [DOI] [PubMed] [Google Scholar]
- 8.Dueholm M, Lundorf E. Transvaginal ultrasound or MRI for diagnosis of adenomyosis. Curr Opin Obstet Gynecol. 2007;19(6):505–512. doi: 10.1097/GCO.0b013e3282f1bf00. [DOI] [PubMed] [Google Scholar]
- 9.Yeniel O, et al. Adenomyosis: prevalence, risk factors, symptoms and clinical findings. Clin Exp Obstet Gynecol. 2007;34(3):163–167. [PubMed] [Google Scholar]
- 10.Maheshwari A, et al. Adenomyosis and subfertility: a systematic review of prevalence, diagnosis, treatment and fertility outcomes. Hum Reprod Update. 2012;18(4):374–392. doi: 10.1093/humupd/dms006. [DOI] [PubMed] [Google Scholar]
- 11.Abu Hashim H, et al. The prevalence of adenomyosis in an infertile population: a cross-sectional study. Reprod Biomed Online. 2020;40(6):842–850. doi: 10.1016/j.rbmo.2020.02.011. [DOI] [PubMed] [Google Scholar]
- 12.Puente JM, 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. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Vercellini P, et al. Uterine adenomyosis and in vitro fertilization outcome: a systematic review and meta-analysis. Hum Reprod. 2014;29(5):964–977. doi: 10.1093/humrep/deu041. [DOI] [PubMed] [Google Scholar]
- 14.Younes G, Tulandi T. Effects of adenomyosis on in vitro fertilization treatment outcomes: a meta-analysis. Fertil Steril. 2017;108(3):483–490.e3. doi: 10.1016/j.fertnstert.2017.06.025. [DOI] [PubMed] [Google Scholar]
- 15.Mavrelos D, et al. The impact of adenomyosis on the outcome of IVF–embryo transfer. Reprod Biomed Online. 2017;35(5):549–554. doi: 10.1016/j.rbmo.2017.06.026. [DOI] [PubMed] [Google Scholar]
- 16.Nirgianakis K, et al. Fertility, pregnancy and neonatal outcomes of patients with adenomyosis: a systematic review and meta-analysis. Reprod Biomed Online. 2021;42(1):185–206. doi: 10.1016/j.rbmo.2020.09.023. [DOI] [PubMed] [Google Scholar]
- 17.Horton J, et al. Reproductive, obstetric, and perinatal outcomes of women with adenomyosis and endometriosis: a systematic review and meta-analysis. Hum Reprod Update. 2019;25(5):592–632. doi: 10.1093/humupd/dmz012. [DOI] [PubMed] [Google Scholar]
- 18.Huang Y, et al. 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. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Bruun MR, et al. Endometriosis and adenomyosis are associated with increased risk of preterm delivery and a small-for-gestational-age child: a systematic review and meta-analysis. Acta Obstet Gynecol Scand. 2018;97(9):1073–1090. doi: 10.1111/aogs.13364. [DOI] [PubMed] [Google Scholar]
- 20.Razavi M, et al. Systematic review and meta-analysis of adverse pregnancy outcomes after uterine adenomyosis. Int J Gynaecol Obstet. 2019;145(2):149–157. doi: 10.1002/ijgo.12799. [DOI] [PubMed] [Google Scholar]
- 21.Vannuccini S, et al. Role of medical therapy in the management of uterine adenomyosis. Fertil Steril. 2018;109(3):398–405. doi: 10.1016/j.fertnstert.2018.01.013. [DOI] [PubMed] [Google Scholar]
- 22.Grimbizis GF, Mikos T, Tarlatzis B. Uterus-sparing operative treatment for adenomyosis. Fertil Steril. 2014;101(2):472–487. doi: 10.1016/j.fertnstert.2013.10.025. [DOI] [PubMed] [Google Scholar]
- 23.Younes G, Tulandi T. Conservative Surgery for Adenomyosis and Results: A Systematic Review. J Minim Invasive Gynecol. 2018;25(2):265–276. doi: 10.1016/j.jmig.2017.07.014. [DOI] [PubMed] [Google Scholar]
- 24.Rocha TP, et al. Fertility-Sparing Treatment of Adenomyosis in Patients With Infertility: A Systematic Review of Current Options. Reprod Sci. 2018;25(4):480–486. doi: 10.1177/1933719118756754. [DOI] [PubMed] [Google Scholar]
- 25.Tan J, et al. Reproductive Outcomes after Fertility-Sparing Surgery for Focal and Diffuse Adenomyosis: A Systematic Review. J Minim Invasive Gynecol. 2018;25(4):608–621. doi: 10.1016/j.jmig.2017.12.020. [DOI] [PubMed] [Google Scholar]
- 26.Xie M, et al. Elasticity of adenomyosis is increased after GnRHa therapy and is associated with spontaneous pregnancy in infertile patents. J Gynecol Obstet Hum Reprod. 2019;48(10):849–853. doi: 10.1016/j.jogoh.2019.05.003. [DOI] [PubMed] [Google Scholar]
- 27.Goldberger MA, Marshak RH, Hermel M. Roentgen diagnosis of adenomyosis uteri. Am J Obstet Gynecol. 1949;57(3):563–568. doi: 10.1016/0002-9378(49)90243-4. [DOI] [PubMed] [Google Scholar]
- 28.Stamatopoulos CP, et al. Value of magnetic resonance imaging in diagnosis of adenomyosis and myomas of the uterus. J Minim Invasive Gynecol. 2012;19(5):620–626. doi: 10.1016/j.jmig.2012.06.003. [DOI] [PubMed] [Google Scholar]
- 29.Novellas S, et al. MRI Characteristics of the Uterine Junctional Zone: From Normal to the Diagnosis of Adenomyosis. Am J Roentgenol. 2011;196(5):1206–1213. doi: 10.2214/AJR.10.4877. [DOI] [PubMed] [Google Scholar]
- 30.Kepkep K, et al. Transvaginal sonography in the diagnosis of adenomyosis: which findings are most accurate? Ultrasound Obstet Gynecol. 2007;30(3):341–345. doi: 10.1002/uog.3985. [DOI] [PubMed] [Google Scholar]
- 31.Dueholm M. Transvaginal ultrasound for diagnosis of adenomyosis: a review. Best Pract Res Clin Obstet Gynaecol. 2006;20(4):569–582. doi: 10.1016/j.bpobgyn.2006.01.005. [DOI] [PubMed] [Google Scholar]
- 32.Struble J, Reid S, Bedaiwy MA. Adenomyosis: A Clinical Review of a Challenging Gynecologic Condition. J Minim Invasive Gynecol. 2016;23(2):164–185. doi: 10.1016/j.jmig.2015.09.018. [DOI] [PubMed] [Google Scholar]
- 33.Cakmak H, Taylor HS. Implantation failure: molecular mechanisms and clinical treatment. Hum Reprod Update. 2011;17(2):242–253. doi: 10.1093/humupd/dmq037. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Harada T. The Impact of Adenomyosis on Women's Fertility. Obstet Gynecol Surv. 2016;71(9):557–568. doi: 10.1097/OGX.0000000000000346. [DOI] [PMC free article] [PubMed] [Google Scholar]