Impact of adenomyosis on pregnancy outcomes: a retrospective consecutive cohort study.

OBJECTIVE: This retrospective study explored the potential connection between adenomyosis and pregnancy outcomes. PATIENTS AND METHODS: A study included data from a total of 1,208 pregnancies. The adenomyosis group included 334 pregnant women with adenomyosis, and women in the control group (n=874) had uncomplicated pregnancies. Data on pregnancy complications and maternal and neonatal outcomes were compared. RESULTS: The incidence of gestational hypertension, gestational diabetes, and placenta previa was higher in the adenomyosis group compared to the control group (p<0.05). Adenomyosis was linked to a higher risk of postpartum hemorrhage (1,000-1,500 ml) but a lower risk of premature rupture of membranes (PROM) (p<0.05). Diagnosis of adenomyosis correlated with increased incidence of low fetal weight (20.3% vs. 21.3%, p<0.05) and a low APGAR score at 1 min (p<0.05). CONCLUSIONS: Adenomyosis correlated with a higher incidence of gestational hypertension, placenta previa, and gestational diabetes. At the same time, adenomyosis correlated with a significantly lower incidence of PROM compared to uncomplicated pregnancy. There was a significant increase in the incidence of postpartum hemorrhage and a higher risk of low fetal weight and lower APGAR score at 1 min in pregnancies with adenomyosis.

Epidemiological characteristics of suspected adenomyosis in the Chinese physical examination population: a nested case-control study.

OBJECTIVES: We aimed to explore the epidemiological characteristics of suspected adenomyosis within a physical examination population in China. DESIGN: A retrospective, nested case-control study; we matched healthy people and those with potential adenomyosis on a 1:2 ratio by age. SETTING: A tertiary hospital health management centre. PARTICIPANTS: We included 15-60 years old women who underwent at least one uterine examination from October 2017 to December 2020, excluding those who had undergone hysterectomy and menopause. PRIMARY AND SECONDARY OUTCOME MEASURES: We estimated the incidence and prevalence rate of suspected adenomyosis. Conditional logistic regression was used to estimate associations between serum biomarkers and potential adenomyosis. Areas under the receiver-operating characteristic curves (AUC) were used to determine the cut-off point of the cancer antigen 125 (CA125) level for suspected adenomyosis. RESULTS: A total of 30 629 women had uterus-related imaging examinations; 877 had suspected adenomyosis. The standardised incidence and prevalence of suspected adenomyosis was 1.32% and 2.35%, respectively, for all age groups. The conditional logistic regression analysis results showed that total bilirubin≥18.81 µmol/L (HR: 2.129; 95% CI 1.067 to 4.249; p<0.0321) and CA125 levels (HR: 1.014; 95% CI 1.002 to 4.731; p<0.0273) were positively correlated with onset of suspected adenomyosis; body mass index>24 kg/m2 (HR: 1.262; 95% CI 1.055 to 1.511; p<0.0109), CA125 levels (HR: 1.007; 95% CI 1.006 to 1.009; p<0.0001), and blood platelet levels (HR: 1.002; 95% CI 1 to 1.003; p<0.0141) were positively correlated with potential adenomyosis. The optimal cut-off of CA125 for new suspected adenomyosis was 10.714 U/mL, with a sensitivity of 77.42%, specificity of 53.76%, and AUC of 0.7841 (95% CI 0.7276 to 0.8407). CONCLUSIONS: The disease burden of suspected adenomyosis remains huge and can be informed by biomarkers. The disease-specific threshold of CA125 will support further preventive strategy development in population. TRIAL REGISTRATION NUMBER: ChiCTR2100049520, 2021/8/2.

Proposal for targeted, neo-evolutionary-oriented, secondary prevention of early-onset endometriosis and adenomyosis. Part I: pathogenic aspects.

The potential for repeated ovulation and menstruation is thought to have provided a Darwinian advantage during the Palaeolithic. Reproductive conditions remained relatively stable until the pre-industrial era, characterized by late menarche, very young age at first birth, multiple pregnancies, and prolonged periods of lactational amenorrhoea. For hundreds of thousands of years, menstruators experienced few ovulatory cycles, even though they were genetically adapted to ovulate and menstruate every month. In the post-industrial era, the age at menarche gradually declined, the age at first birth progressively increased, and breastfeeding became optional and often of short duration. This created a mismatch between genetic adaptation and socio-environmental evolution, so that what was initially a probable reproductive advantage subsequently contributed to increased susceptibility to diseases associated with lifetime oestrogen exposure, such as ovarian, endometrial and breast cancer and, hypothetically, also those associated with the number of ovulatory menstruations, such as endometriosis and adenomyosis. The incidence of endometriosis shows a steep and progressive increase around the age of 25 years, but given the consistently reported delay in diagnosis, the actual incidence curve should be shifted to the left, supporting the possibility that the disease has its roots in adolescence. This raises the question of whether, from an evolutionary point of view, anovulation and amenorrhoea should not still be considered the physiological state, especially in the postmenarchal period. However, an increase in the frequency of endometriosis in recent decades has not been demonstrated, although this deserves further epidemiological investigation. In addition, as endometriosis occurs in a minority of individuals exposed to retrograde menstruation, other important pathogenic factors should be scrutinised. Research should be resumed to explore in more detail the transtubal reflux of not only blood, but also endometrial cells, and whether they are systematically present in the peritoneal fluid after menstruation. If repetitive ovulatory menstruation during the early reproductive years is shown to increase the risk of endometriosis and adenomyosis development and progression in susceptible individuals, hormonal interventions could be used as secondary prevention in symptomatic adolescents.

Clinical characteristics and outcomes of women with adenomyosis pain during pregnancy: a retrospective study.

OBJECTIVES: Adenomyosis is associated with unfavorable perinatal outcomes, and recent case reports show that some women with adenomyosis experience pain at the adenomyosis lesion during pregnancy and have detrimental perinatal outcomes. This study aimed to clarify the clinical characteristics of this pain and perinatal outcomes associated with this phenomenon. METHODS: This was a single-center retrospective analysis of pregnant women with adenomyosis. The incidence of pain onset at adenomyosis lesions, defined as persistent pain at the adenomyosis site with administration of analgesics for pain relief, and its association with perinatal outcomes were analyzed. RESULTS: Among 91 singleton pregnancies with adenomyosis, 12 pregnancies (13.2 %) presented with pain. One pregnancy resulted in second-trimester miscarriage, and 5 of the 11 pregnancies (45 %) developed preeclampsia, which resulted in preterm delivery, and 3 of the 12 pregnancies (25 %) achieved term delivery. The incidence of preeclampsia and preterm delivery was higher in those who experienced pain than in those without (45 % [5/11] vs. 15 % [11/74]; p<0.05, and 73 % [8/11] vs. 34 % [25/74]; p<0.05, respectively). Among women with pain, the maximum C-reactive protein level was significantly higher in women who developed preeclampsia than in those who did not (5.45 vs. 0.12 mg/dL, p<0.05). CONCLUSIONS: Our study revealed that adenomyosis can cause pain in over one of eight pregnancies with adenomyosis, which may be associated with the increased incidence of preeclampsia resulting in preterm delivery. Women with pain, especially those with high C-reactive protein levels, may be at high risk for future development of preeclampsia and consequent preterm delivery.

Differences in the incidence of obstetric complications depending on the extent and location of adenomyosis lesions.

OBJECTIVES: Although adenomyosis is reportedly associated with adverse pregnancy outcomes, clinical factors related to the high risk of obstetric complications are unclear. This study aimed to elucidate the characteristics of adenomyosis lesions associated with the increased incidence of obstetric complications based on imaging findings. METHODS: This was a retrospective, observational cohort study conducted in a tertiary perinatal care center. Eighty-eight singleton pregnant women with adenomyosis were included in the study. Based on magnetic resonance imaging or ultrasonography before and/or during pregnancy, patients were classified according to three types of image characteristics: the extent of adenomyosis lesion (focal type or diffuse type), location of the lesion (extrinsic type, intrinsic type, or indeterminate type), the positional relationship between the lesion and the placenta (placenta distant from adenomyosis or placenta over adenomyosis), and the incidence of obstetric complications were examined. RESULTS: Patients with diffuse type adenomyosis are significantly more likely to have spontaneous second-trimester miscarriage (diffuse type vs. focal type: 16.7 vs. 0%, p < .01), preterm premature rupture of membranes (19.4 vs. 1.9%, p < .01), and preeclampsia (25.0 vs. 7.7%, p = .02), as compared to those with focal type adenomyosis. In a comparison of the three location types, the incidence of placental malposition was higher in patients with the extrinsic type adenomyosis (extrinsic type vs. intrinsic type vs. indeterminate type: 20.0 vs. 6.7 vs. 2.3%, p = .03). Comparisons between the types of the placenta over or distant from adenomyosis lesion displayed no significant differences in the frequencies of obstetric complications. CONCLUSIONS: We demonstrated that the frequency of obstetric complications related to adenomyosis varies depending on the extent and location of the lesion; patients with diffuse type adenomyosis have an increased risk of spontaneous second-trimester miscarriage, preterm premature rupture of membranes, and preeclampsia, while patients with extrinsic type adenomyosis have an increased risk of placental malposition. Imaging evaluation of adenomyosis prior to conception or early in pregnancy may be useful for the obstetrical risk assessment among patients with adenomyosis.

Impact of adenomyosis on perinatal outcomes: a large cohort study (JSOG database).

BACKGROUND: A previous study investigated the effect of adenomyosis on perinatal outcomes. Some studies have reported varying effect of adenomyosis on pregnancy outcomes in some patients and dependence on the degree and subtype of uterine lesions. To elucidate the impact of adenomyosis on perinatal outcomes. METHODS: This large-scale cohort study used the perinatal registry database of the Japan Society of Obstetrics and Gynecology. A dataset of 203,745 mothers who gave birth between January 2020 and December 2020 in Japan was included in the study. The participants were divided into two groups based on the presence or absence of adenomyosis. Information regarding the use of fertility treatment, delivery, obstetric complications, maternal treatments, infant, fetal appendages, obstetric history, underlying diseases, infectious diseases, use of drugs, and maternal and infant death were compared between the groups. RESULTS: In total, 1,204 participants had a history of adenomyosis and 151,105 did not. The adenomyosis group had higher rates of uterine rupture (0.2% vs. 0.01%, P = 0.02) and placenta accreta (2.0% vs. 0.5%, P < 0.001) than the non-adenomyosis group. A history of adenomyosis (odds ratio: 2.26; 95% confidence interval: 1.43-3.27; P < 0.001), uterine rupture (odds ratio: 3.45; 95% confidence interval: 0.89-19.65; P = 0.02), placental abruption (odds ratio: 2.11; 95% confidence interval: 1.27-3.31; P < 0.01), and fetal growth restriction (odds ratio: 2.66; 95% confidence interval: 2.00-3.48; P < 0.01) were independent risk factors for placenta accreta. CONCLUSION: Adenomyosis in pregnancies is associated with an increased risk of placenta accreta, uterine rupture, placental abruption, and fetal growth restriction. TRIAL REGISTRATION: Institutional Review Board of Tottori University Hospital (IRB no. 21A244).

The association between uterine adenomyosis and adverse obstetric outcomes: A propensity score-matched analysis.

INTRODUCTION: This study examined obstetric outcomes in patients diagnosed with uterine adenomyosis. MATERIAL AND METHODS: This historical cohort study queried the Healthcare Cost and Utilization Project's National Inpatient Sample. The study population was all hospital deliveries in women aged 15-54 years between January 2016 and December 2019. The exposure was a diagnosis of uterine adenomyosis. The main outcome measures were obstetric characteristics, including placenta previa, placenta accreta spectrum, and placental abruption. Secondary outcomes were delivery complications including severe maternal morbidity. Analytic steps to assess these outcomes included (i) a 1-to-N propensity score matching to mitigate and balance prepregnancy confounders to assess obstetric characteristics, followed by (ii) an adjusting model with preselected pregnancy and delivery factors to assess maternal morbidity. Sensitivity analyses were also performed with restricted cohorts to account for prior uterine scar, uterine myoma, and extra-uterine endometriosis. RESULTS: After propensity score matching, 5430 patients with adenomyosis were compared to 21 720 patients without adenomyosis. Adenomyosis was associated with an increased odds of placenta accreta spectrum (adjusted-odds ratio [aOR] 3.07, 95% confidence interval [CI] 2.01-4.70), placenta abruption (aOR 3.21, 95% CI: 2.60-3.98), and placenta previa (aOR 5.08, 95% CI: 4.25-6.06). Delivery at <32 weeks of gestation (aOR 1.48, 95% CI: 1.24-1.77) and cesarean delivery (aOR 7.72, 95% CI: 7.04-8.47) were both increased in women with adenomyosis. Patients in the adenomyosis group were more likely to experience severe maternal morbidity at delivery compared to those in the nonadenomyosis group (aOR 1.86, 95% CI: 1.59-2.16). Results remained robust in the aforementioned several sensitivity analyses. CONCLUSIONS: This national-level analysis suggests that a diagnosis of uterine adenomyosis is associated with an increased risk of placental pathology (placenta accreta spectrum, placenta abruption, and placental previa) and adverse maternal outcomes at delivery.

Relation between adenomyosis and elastographic characteristics of the cervix.

STUDY QUESTION: Is there a possible etiologic link between cervical stiffness and adenomyosis? SUMMARY ANSWER: Women with adenomyosis have a stiffer internal cervical os than those without adenomyosis. WHAT IS KNOWN ALREADY: An increased myometrial contractility during menses, leading to breaches in the endometrial basal lamina and subsequent infiltration of endometrial cells into the myometrium, has been proposed as a possible pathogenic mechanism for adenomyosis. Intense menstrual pain has already been shown to be associated with an increased stiffness, at elastography, of the internal cervical os. STUDY DESIGN, SIZE, DURATION: A cross-sectional study on 275 women was performed between 1 February and 31 July 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Among the participants, 103 were and 172 women were not affected by adenomyosis as evaluated by ultrasonography. General and clinical characteristics of the patients were collected. Strain elastography was used to document tissue stiffness at different regions of interest of the cervix, i.e. the internal cervical os, the middle cervical canal, the anterior and the posterior cervical compartment. Tissue stiffness was expressed as a colour score from 0.1 = blue/violet (high stiffness) to 3.0 = red (low stiffness). Simple and multiple logistic regression analyses were used to evaluate the relation between the presence of adenomyosis, as the dependent variable, and independent factors. MAIN RESULTS AND THE ROLE OF CHANCE: Women with adenomyosis had a higher prevalence (P = 0.0001) and intensity (P = 0.0001) of pain during menses, between menses and at intercourse compared to control. The internal cervical os colour score was lower (higher stiffness) in women with adenomyosis (0.55 ± 0.29 versus 0.67 ± 0.26; P = 0.001) and the middle cervical canal/internal cervical os colour score ratio was greater (3.32 ± 4.36 versus 2.59 ± 4.99; P = 0.008), compared to controls. Upon logistic regression modelling (R2 = 0.077), the internal cervical os stiffness was an independent factor related to adenomyosis (odds ratio (OR) 0.220, 95% CI 0.077, 0.627; P = 0.005) along with age (P = 0.005) and the use of gonadal steroid therapies (P = 0.002). We obtained the same results using a different logistic regression model (R2 = 0.069), by substituting the internal cervical os stiffness with the ratio of the middle cervical canal/internal cervical os stiffness (OR 1.157, 95% CI 1.024, 1.309; P = 0.019). LIMITATIONS, REASONS FOR CAUTION: Women did not undergo surgery therefore we have no histological confirmation of the adenomyosis diagnosis. Strain elastography is a semiquantitative analysis and can be conditioned by the force applied by the operator during the analysis. The data were obtained mainly in White women in a single centre. WIDER IMPLICATIONS OF THE FINDINGS: To the best of our knowledge, this is the first study indicating that women with adenomyosis have an increased stiffness of the internal cervical os. The results indicate that a stiff internal cervical os, as determined by elastography, is a possible contributor to the development of adenomyosis. These findings may have clinical significance and should prompt further investigation. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Factors associated with deep infiltrating endometriosis, adenomyosis and ovarian endometrioma.

INTRODUCTION: To compare epidemiological features and clinical presentations of deep infiltrating endometriosis with endometrioma and adenomyosis, as well as to identify risk factors for the respective histologically confirmed conditions. METHOD: Patients undergoing index surgery at the National University Hospital, Singapore for endometriosis or adenomyosis over a 7-year period-from 2015 to 2021-were identified from hospital databases using the Table of Surgical Procedures coding. Social and epidemiological features of cases with histologically confirmed diagnoses of endometrioma only, adenomyosis only, and deep infiltrating endometriosis were compared. Significant variables from univariate analysis were entered into 3 binary multivariate logistic regression models to obtain independent risk factors for: deep infiltrating endometriosis versus endometrioma only, deep infiltrating endometriosis versus adenomyosis only, and adenomyosis only versus endometrioma only. RESULTS: A total of 258 patients were included with 59 ovarian endometrioma only, 47 adenomyosis only, and 152 deep infiltrating endometrioses. Compared to endometrioma only, deep infiltrating endometriosis was associated with higher rates of severe dysmenorrhoea (odds ratio [OR] 2.80, 95% confidence interval [CI] 1.02-7.70) and out-of-pocket private surgical care (OR 4.72, 95% CI 1.85-12.04). Compared to adenomyosis only, deep infiltrating endometriosis was associated with a higher fertility desire (OR 13.47, 95% CI 1.01-180.59) and a lower body mass index (OR 0.89, 95% CI 0.79-0.99). In contrast, heavy menstrual bleeding was the hallmark of adenomyosis, being less common in patients with endometriosis. CONCLUSION: Deep infiltrating endometriosis is associated with severe dysmenorrhoea, pain related to urinary and gastrointestinal tracts, higher fertility desire and infertility rate. Patients with pain symptomatology and subfertility should be referred early to a tertiary centre with the capability to diagnose and manage deep infiltrating endometriosis.

Association of endometriosis and adenomyosis with pregnancy and infertility.

We performed a comprehensive narrative synthesis of systematic reviews with meta-analysis published in the last 5 years on the association of endometriosis and adenomyosis with reproductive and obstetric outcomes. This review aimed to define the information on which to base preconceptional counseling and clarify whether and in which cases pregnant women with endometriosis and adenomyosis should be referred to tertiary care centers and followed as high-risk obstetric patients. Reduced pregnancy and live birth rates and an increased miscarriage rate were observed in women with endometriosis and adenomyosis. The effect was larger in women with adenomyosis than in those with endometriosis. Women with superficial peritoneal and ovarian endometriosis do not appear to be at considerably increased risk of major obstetric and neonatal complications, whereas women with severe endometriosis, whether operated or not, are at several-fold increased risk of placenta previa. Moreover, deep infiltrating endometriosis is a risk factor for spontaneous hemoperitoneum in pregnancy and is associated with surgical complications at cesarean section. Overall, women with adenomyosis are at increased risk of various adverse obstetric outcomes, including preeclampsia, preterm delivery, fetal malpresentation, postpartum hemorrhage, low birth weight, and small for gestational age. Most studies included in the considered systematic reviews are characterized by substantial qualitative and quantitative heterogeneity. This makes a reliable assessment of the available evidence difficult, and caution should be exercised when attempting to derive clinical indications. Nevertheless, women with deep infiltrating endometriosis and severe adenomyosis should be considered at high obstetric risk and can benefit from referral to tertiary care centers where they can be safely followed through pregnancy and delivery. Whether the same should apply also to pregnant women with minimal endometriosis and adenomyosis forms is currently uncertain. Emerging evidence suggests that some adverse reproductive and obstetric outcomes observed in women with endometriosis are, in fact, associated with coexisting adenomyosis.

Endometriosis and adenomyosis in the crosshair: variants of one disorder or fortuitous coincidence.

Adenomyosis and endometriosis share a common origin as both of them result from the development of endometrial tissue outside the endometrium. Despite this, the 2 disorders were until recently considered as 2 different entities notably, because of their different epidemiology. Today, however, new findings regarding core similarities in pathophysiology and endometrial receptivity - not altered in assisted reproductive technology when using frozen embryo transfers - tend to reunite these 2 ailments as variants of 1 disorder.

Prevalence of adenomyosis in women with subfertility: systematic review and meta-analysis.

OBJECTIVE: To determine the prevalence of adenomyosis in women with subfertility. METHODS: A systematic search was conducted in MEDLINE, EMBASE, CINAHL Plus, Google Scholar, PsycINFO and Web of Science Core Collection from database inception to October 2022. The included studies evaluated the prevalence of adenomyosis in women with subfertility, with or without endometriosis and/or uterine fibroids. Secondary analyses were conducted to identify variation in the prevalence of isolated adenomyosis according to geographical location, diagnostic modality, diagnostic criteria, type of ultrasound, ultrasound features of adenomyosis and the use of assisted reproductive technology. RESULTS: Among 21 longitudinal studies evaluating 25 600 women, the overall pooled prevalence of isolated adenomyosis was 10% (95% CI, 6-15%) (I2 = 99.1%; tau2 = 0.12). The pooled prevalence was 1% (95% CI, 0-4%) for adenomyosis with concurrent fibroids (eight studies; I2 = 95.8%; tau2 = 0.03), 6% (95% CI, 3-11%) for adenomyosis with concurrent endometriosis (18 studies; I2 = 98.6%; tau2 = 0.12) and 7% (95% CI, 2-13%) for adenomyosis with concurrent endometriosis and/or fibroids (nine studies; I2 = 98.3%; tau2 = 0.09). The prevalence of isolated adenomyosis varied substantially according to geographical location, with Australia exhibiting the highest pooled prevalence of adenomyosis (19% (95% CI, 12-27%)), which was significantly higher compared with that in Asia (5% (95% CI, 1-12%)). The pooled prevalence of isolated adenomyosis diagnosed using a combination of direct and indirect ultrasound features was 11% (95% CI, 7-16%), whereas it was 0.45% (95% CI, 0-1%) in the study in which only an indirect feature was used as the diagnostic criterion. CONCLUSION: One in 10 women with subfertility have a diagnosis of isolated adenomyosis. The prevalence of adenomyosis varies according to the presence of concurrent endometriosis and/or fibroids. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Cannabis smoking, tobacco cigarette smoking, and adenomyosis risk.

OBJECTIVE: To investigate cannabis smoking and tobacco cigarette smoking in relation to adenomyosis risk. DESIGN: We used data from a case-control study of adenomyosis conducted among enrollees ages 18-59 years of an integrated health care system in Washington State. The case-control study used 2 control groups given the challenge of selecting noncases when cases are diagnosed by hysterectomy. SUBJECTS: Cases (n = 386) were enrollees with incident, pathology-confirmed adenomyosis diagnosed between April 1, 2001, and March 31, 2006. The 2 control groups comprised hysterectomy controls (n = 233) with pathology-confirmed absence of adenomyosis and population controls (n = 323) with an intact uterus selected randomly from the health care system population and frequency matched to cases on age. EXPOSURE: Detailed data on cannabis and tobacco cigarette smoking history were ascertained through in-person structured interviews, allowing estimation of joint-years of cannabis smoking and pack-years of tobacco cigarette smoking. MAIN OUTCOME MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between cannabis smoking, tobacco cigarette smoking, and adenomyosis were estimated using multivariable unconditional logistic regression. Analyses were adjusted for age, reference year, menarche age, education, and pack-years of cigarette smoking (or joint-years of cannabis smoking). RESULTS: No association was observed between cannabis smoking history and adenomyosis risk. However, we did observe the suggestion of an association between ever tobacco cigarette smoking and adenomyosis risk, comparing cases to hysterectomy controls (OR, 1.3; 95% CI, 0.9-1.9) and population controls (OR, 1.2; 95% CI, 0.8-1.8). Our data suggested a 50% increased odds of adenomyosis with >15 pack-years of smoking (vs. never smoking), comparing cases to hysterectomy controls (OR, 1.5; 95% CI, 0.9-2.6; Ptrend=.135). The suggestion of a 40% increased adenomyosis odds was observed with smoking >5-15 pack-years (vs. never smoking), comparing cases to population controls (OR, 1.4; 95% CI, 0.8-2.4; Ptrend=0.136). CONCLUSION: In the first study of cannabis smoking and adenomyosis risk, no association was observed. However, our data suggested an increased odds of adenomyosis with history of tobacco cigarette smoking. Further research is warranted to replicate our results given the substantial morbidity with adenomyosis and frequency of cigarette smoking and recreational and medical cannabis use.

The ADENO study: ADenomyosis and its Effect on Neonatal and Obstetric outcomes: a retrospective population-based study.

BACKGROUND: Adenomyosis is a benign gynecologic condition arising from the uterine junctional zone. Recent studies suggest a relationship between adenomyosis and adverse obstetrical outcomes, but evidence remains conflicting. There is no large-scale study investigating obstetrical outcomes in women with adenomyosis using the gold standard of histopathologic diagnosis. OBJECTIVE: This study aimed to investigate the prevalence of adverse obstetrical and neonatal outcomes in women with histopathologic adenomyosis and that of the general (Dutch) population. STUDY DESIGN: This retrospective population-based study used 2 Dutch national databases (Perined, the perinatal registry, and the nationwide pathology databank [Pathologisch Anatomisch Landelijk Geautomiseerd Archief], from 1995 to 2018) to compare obstetrical outcomes in women before histopathologic adenomyosis diagnosis to the general Dutch population without registered histopathologic adenomyosis. The adjusted odds ratios (95% confidence interval) were calculated for adverse obstetrical outcomes. The outcomes were adjusted for maternal age, parity, ethnicity, year of registered birth, induction of labor, hypertensive disorders in previous pregnancies, multiple gestation, and low socioeconomic status. RESULTS: The pregnancy outcomes of 7925 women with histopathologic adenomyosis were compared with that of 4,615,803 women without registered adenomyosis. When adjusted for confounders, women with adenomyosis had adjusted odds ratios of 1.37 (95% confidence interval, 1.25-1.50) for hypertensive disorders, 1.37 (95% confidence interval, 1.25-1.51) for preeclampsia, 1.15 (95% confidence interval, 1.07-1.25) for small-for-gestational-age infants, 1.54 (95% confidence interval, 1.41-1.68) for emergency cesarean delivery, 1.24 (95% confidence interval, 1.12-1.37) for failure to progress, 1.29 (95% confidence interval, 1.10-1.48) for placental retention, and 1.23 (95% confidence interval, 1.10-1.38) for postpartum hemorrhage. No increased risk of HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, placental abruption, or operative vaginal delivery or need for oxytocin stimulation was found. CONCLUSION: Women with a histopathologic diagnosis of adenomyosis showed an increased prevalence of hypertensive disorders of pregnancy and small-for-gestational-age infants, failure to progress in labor, and placental retention compared with the general population in previous pregnancies. This suggests that uterine (contractile) function in labor and during pregnancy is impaired in women with adenomyosis.

Breastfeeding history and adenomyosis risk using a novel case-control study design.

OBJECTIVE: To evaluate the association between breastfeeding history, including lifetime exclusive breastfeeding, and risk of adenomyosis. DESIGN: We used data from a case-control study designed with 2 control groups to address the challenge of selecting noncases for a valid epidemiologic study when cases are identified by hysterectomy. The case-control study was conducted among premenopausal and postmenopausal enrollees aged 18-59 years in a large, integrated health care system in western Washington state. PATIENT(S): Cases were enrollees with incident, pathology-confirmed adenomyosis diagnosed during 2001-2006 (n = 386). The 2 control groups were as follows: (1) randomly selected age-matched enrollees with intact uteri ("population controls," n = 323) and (2) hysterectomy controls (n = 233). INTERVENTION(S): Data on breastfeeding history were collected by in-person interviews. For each reported live birth, participants were asked whether they breastfed, along with infant age at supplemental feeding introduction and breastfeeding discontinuation. MAIN OUTCOME MEASURE(S): Among participants with at least 1 live birth (330 cases, 246 population controls, and 198 hysterectomy controls), we used unconditional logistic regression to estimate adjusted odds ratios and 95% confidence intervals (CIs) for the associations between the following: (1) ever breastfeeding, (2) ever breastfeeding for ≥8 weeks, (3) lifetime breastfeeding, and (4) lifetime exclusive breastfeeding and risk of adenomyosis. Analyses were adjusted for age, reference year, smoking, education, and parity. RESULT(S): In analyses comparing cases with population controls, we observed a 40% decreased odds of adenomyosis with a history of ever breastfeeding (adjusted odds ratio, 0.6; 95% CI, 0.3-1.0) and breastfeeding for ≥8 weeks (adjusted odds ratio, 0.6; 95% CI, 0.4-0.8). The strongest associations, 60%-70% decreased odds of adenomyosis, were observed with ≥12 months of lifetime breastfeeding (vs. <3 months) (adjusted odds ratio, 0.4; 95% CI, 0.2-0.6) and 9 to <12 months of lifetime exclusive breastfeeding (vs. <3 months) (adjusted odds ratio, 0.3; 95% CI, 0.2-0.6), comparing cases to population controls. In analyses using hysterectomy controls, we observed similar patterns of associations slightly attenuated in magnitude. CONCLUSION(S): Breastfeeding history was associated with a 40% decreased odds of adenomyosis, a condition that can confer substantial morbidity and requires hysterectomy for definitive treatment. The consistency of our findings with that of a previous study lends support that breastfeeding may modify risk of adenomyosis.

How adenomyosis changes throughout pregnancy: A retrospective cohort study.

OBJECTIVE: To study how adenomyosis changes during pregnancy and to possibly correlate these changes to maternal and fetal outcomes. METHODS: Retrospective exploratory cohort study including 254 women with a pre-conceptional/first-trimester scan to document adenomyosis and known obstetric outcome. If visible, adenomyosis signs were documented in each trimester and postpartum. Mann-Whitney U tests or χ2 tests were used for continuous and categorical variables, respectively. RESULTS: A globular uterus was reported in 79% (n = 52) of women with adenomyosis in the first trimester, in 38% (n = 20) and 2% (n = 1) of women in the second and third trimesters, respectively, and postpartum in 77% (n = 34) of women. Asymmetrical thickening (n = 20, 30%) and cysts (n = 15, 23%) were only visible in 1st trimester. Adenomyosis was associated with miscarriage (odds ratio [OR] 5.9, 95% confidence interval [CI] 2.4-14.9, P < 0.001) also in normal conception only (OR 5.1, 95% CI 1.8-14.2, P = 0.002) or adjusting for maternal age (adjusted OR 5.9, 95% CI 2.3-15.2, P < 0.001). Gestational age at delivery was lower in adenomyosis (P = 0.004); the cesarean section rate was higher than in controls (OR 2.5, 95% CI 1.3-4.8, P = 0.007) also adjusting for age (adjusted OR 2.07, 95% CI 1.06-4.08, P = 0.035). CONCLUSIONS: Signs of adenomyosis were visible but progressively disappeared in pregnancy; adenomyosis was associated with an increased risk of early miscarriage. Prospective studies are needed to confirm our results.

[Labor progression characteristics of primiparous term singleton pregnant women complicated with adenomyosis].

Objective: To analyze the labor progression characteristics of primiparous term singleton pregnant women with adenomyosis. Methods: From April 2014 to May 2021, pregnant women underwent regular antenatal examination in Peking University Third Hospital were enrolled in this retrospective study, 109 primiparous term pregnant women with adenomyosis who underwent singleton, primipara, cephalic and vaginal delivery were referred as the adenomyosis group, while 109 pregnant women without adenomyosis primiparous term pregnant women at the same time were referred as the control group. The general clinical information, labor process intervention, pregnancy outcomes and labor course time of the two groups were analyzed. Results: (1) General clinical conditions: the pre-pregnancy uterine volume of the adenomyosis group was larger than that of the control group [(66.8±23.7) vs (41.4±13.1) cm3, P<0.05]. The proportion of assisted reproductive pregnancy and endometriosis in the adenomyosis group were higher than those in the control group [31.2% (34/109) vs 7.3% (8/109); 31.2% (34/109) vs 5.5% (6/109); all P<0.05]. There were no significant differences in maternal age, gestational age at delivery, pre-pregnancy body mass index, gestational weight gain, gravidity, incidence of pregnancy complications (gestational diabetes mellitus, pre-eclampsia and thyroid diseases) and premature rupture of membranes between the two groups (all P>0.05). (2) Labor process intervention and maternal and fetal outcomes: postpartum hemorrhage was higher in the adenomyosis group than the control group (median: 300 vs 260 ml, P=0.018). There were no significant differences in the proportion of labor onset, use of oxytocin, artificial rupture of membranes, perineal laceration Ⅲ and above, episiotomy, newborn weight and 1-minute Apgar score between the two groups (all P>0.05). (3) Time of labor process: there were no significant differences between the two groups in the time required for the first stage, third stage, total stage and cervical dilation 0-1, 1-2, 2-3, 3-4, 4-5, 5-6, 6-7 cm (all P>0.05). The time required for cervical dilation 7-8, 8-9, 9-10 cm and the second stage of labor in adenomyosis group (median: 20, 18, 15 and 12 minutes, respectively) were shorter than those of the control group (median: 23, 23, 23 and 26 minutes, respectively), and the differences were statistically significant (all P<0.05). (4) The effect of endometriosis on labor: there was no significant difference in the effect of endometriosis on labor in adenomyosis group (P>0.05). Conclusions: The labor process of primiparous term pregnant women with adenomyosis is significantly accelerated after the cervical dilatation for 7 cm, which should be closely observed. The third stage of labor course is managed aggressively with drugs to prevent postpartum hemorrhage.

Cardiometabolic profiles in women with adenomyosis.

The aim of this study was to investigate the reproductive profiles, metabolic parameters and cardiometabolic risk assessed by surrogate indexes in women with adenomyosis. Ninety-six premenopausal women who were diagnosed with adenomyosis by transvaginal ultrasound and 97 age-body mass index (BMI) matched controls with normal ultrasound during routine examination were included. Women with adenomyosis were more likely to have higher gravidity and had more abortions than women without adenomyosis. Regarding the individual metabolic syndrome components, the adenomyosis group was more likely to have higher prevalence of hypertension, low HDL-C and central obesity. No significant difference was found between the groups in terms of visceral adiposity index, lipid accumulation product and fatty liver index. Only higher blood pressure (BP) remained statistically significant after adjustment for confounding factors in multivariate analysis. Women with adenomyosis had remarkably high risk of hypertension. It may be advisable to monitor their BP closely.Impact StatementWhat is already known on this subject? The only anthropometric characteristic assessed in women in relation to adenomyosis is body mass index (BMI). A case-control study showed that women who are obese are more likely to have adenomyosis. The gravidity, number of spontaneous abortions and previous uterine surgeries such as dilatation and curettage (D&C) and caesarean section were found significantly associated with adenomyosis.What do the results of this study add? A remarkable finding of our study was the increased incidence of higher systolic BP in women with adenomyosis. No difference was observed in adiposity indices between women with and without adenomyosis. Higher prevalence of central obesity and lower HDL-C levels were seen in women with adenomyosis.What are the implications of these findings for clinical practice and/or further research? The study identifies that adenomyosis is associated with an increased risk of hypertension, and women with adenomyosis may be monitored closely for blood pressure changes. Our report also provides novel information about the metabolic risk profiles associated with adenomyosis.

Adenomyosis decreases the live birth rate but may not affect perinatal outcomes in assisted reproductive cycles.

OBJECTIVE: To determine if uterine adenomyosis is associated with worse perinatal outcomes in ovum donation assisted reproductive treatment cycles. MATERIALS AND METHODS: A multicenter and retrospective cohort study in which a total of 3307 patients undergoing an ovum donation cycle in 2018-2019 were included and divided into two groups: adenomyosis (n = 179) and controls (n = 3128). Clinical, obstetrical, and perinatal outcomes were analyzed. RESULTS: A lower live birth rate per embryo transfer was observed in women diagnosed with adenomyosis versus control women: 67/179 (37%) versus 1560/3128 (49.9%), respectively (odds ratio 0.6, 95% confidence interval 0.43-0.83, P = 0.002). There was no statistically significant difference in childbirth delivery method (vaginal versus cesarean section) between the adenomyosis and control groups. Mean gestational age at the time of delivery, newborn length and weight, and incidences of low birth weight, preterm birth, and admission to the neonatal intensive care unit did not differ between the two groups. In addition, in vitro fertilization and perinatal outcomes were similar in patients with diffuse compared with focal adenomyosis. CONCLUSIONS: Adenomyosis affects clinical but may not affect perinatal outcomes in ovum donation cycles.

Adenomyosis and infertility.

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.