RESUMO
As the incidence of endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) has been increasing, and has shown young trend. It is crucial to study the fertility-preserving treatment of endometrial lesions and fertility-promoting protocols. Age, obesity, and irregular ovulation are not only high-risk factors for endometrial lesions but also key factors affecting female fertility. Assisted reproductive technology (ART) can significantly improve pregnancy outcomes in patients with AEH and EC after conservative treatment. Based on the existing studies, this article reviews the progress of research on pregnancy outcomes of ART and its influencing factors in such patients. It helps physicians in providing optimal fertility guidance.
Assuntos
Tratamento Conservador , Hiperplasia Endometrial , Neoplasias do Endométrio , Preservação da Fertilidade , Técnicas de Reprodução Assistida , Humanos , Feminino , Neoplasias do Endométrio/terapia , Neoplasias do Endométrio/patologia , Hiperplasia Endometrial/terapia , Hiperplasia Endometrial/patologia , Gravidez , Tratamento Conservador/métodos , Preservação da Fertilidade/métodos , Resultado da Gravidez , Infertilidade Feminina/terapia , Infertilidade Feminina/etiologiaRESUMO
⢠Endometrial hyperplasia can be classified as either hyperplasia without atypia or atypical hyperplasia. ⢠Abnormal uterine bleeding is the most common symptom of endometrial hyperplasia. Transvaginal ultrasound is recommended for initial imaging to evaluate endometrial hyperplasia (evidence level 2+), while transrectal ultrasound is recommended for virgo patients (evidence level 3). ⢠Endometrial biopsy should be used to confirm diagnosis in patients where endometrial lesions are suspected. Effective histological approaches to make definite diagnoses include diagnostic curettage (evidence level 2++), hysteroscopic-guided biopsy (evidence level 2+) and endometrial aspiration biopsy (evidence level 2-). ⢠Progesterone is the preferred medication for the treatment of endometrial hyperplasia without atypia. Compared to oral progestins, placement of a levonorgestrel-releasing intrauterine system (LNG-IUS) has been associated with higher regression rates, lower recurrence rates and fewer adverse events which can be the initial treatment method. (Meta evidence level 1-, RCT evidence level 2+). Ultrasound and endometrial biopsies should be performed every 6 months during treatment to evaluate its effect and treatment should continue until no pathological changes are observed in two consecutive endometrial biopsies. Hysterectomy is not the preferred choice of treatment for patients with endometrial hyperplasia without atypia. ⢠Minimally invasive hysterectomy is indicated for patients with endometrial atypical hyperplasia (evidence level 1+), bilateral fallopian tubes should also be removed (evidence level 2+). In cases where surgery cannot be tolerated, fertility is desired or the patient is younger than 45 years old, medical therapy is recommended (evidence level 3). LNG-IUS is the preferred medical therapy method (evidence level 2+). Endometrial pathologic evaluation should be performed every 3 months during conservative treatments, with adjustments made to dosages or approaches based on observed response to medication. Treatment should continue until no pathological changes are detected in two consecutive endometrial biopsies (evidence level 2++). There is no indication of sentinel lymph nodes biopsy and/or lymphadenectomy for hyperplasia with or without atypia. ⢠Total hysterectomy is recommended to treat patients with recurrent endometrial atypical hyperplasia (evidence level 3); however, medical conservative therapy may be considered for patients hoping to become pregnant in the future. ⢠Patients with fully regressed disease who would like to become pregnant should be advised to seek assistance through assisted reproductive technologies (evidence level 3). ⢠Long-term follow-up is suggested for patients after endometrial hyperplasia treatment (evidence level 2+). Patient education is imperative for improving medication adherence, increasing regression rates and lowering recurrence rates (evidence level 3).
Assuntos
Hiperplasia Endometrial , Humanos , Feminino , Hiperplasia Endometrial/terapia , Hiperplasia Endometrial/patologia , Hiperplasia Endometrial/diagnóstico , Levanogestrel/uso terapêutico , Levanogestrel/administração & dosagem , Progestinas/uso terapêutico , Dispositivos Intrauterinos Medicados , Histeroscopia/métodos , China , Ultrassonografia , Biópsia , Histerectomia , Endométrio/patologia , Curetagem , Progesterona/uso terapêutico , Progesterona/administração & dosagemRESUMO
STUDY QUESTION: What are the pregnancy and obstetric outcomes in women with atypical hyperplasia (AH) or early-stage endometrial cancer (EC) managed conservatively for fertility preservation? SUMMARY ANSWER: The study found a live birth rate of 62% in patients with AH or EC after conservative treatment, with higher level of labour induction, caesarean section, and post-partum haemorrhage. WHAT IS KNOWN ALREADY: Fertility-sparing treatment is a viable option for women with AH or EC during childbearing years, but the outcomes of such treatments, especially regarding pregnancy and obstetrics, need further exploration. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study analysed data from January 2010 to October 2022, involving 269 patients from the French national register of patients with fertility-sparing management of AH/EC. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women above 18 years of age, previously diagnosed with AH/EC, and approved for fertility preservation were included. Patients were excluded if they were registered before 2010, if their treatment began <6 months before the study, or if no medical record on the pregnancy was available. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 95 pregnancies in 67 women were observed. Pregnancy was achieved using ART in 63 cases (66%) and the live birth rate was 62%, with early and late pregnancy loss at 26% and 5%, respectively. In the 59 cases resulting in a live birth, a full-term delivery occurred in 90% of cases; 36% of cases required labour induction and 39% of cases required a caesarean section. The most common maternal complications included gestational diabetes (17%) and post-partum haemorrhaging (20%). The average (±SD) birthweight was 3110 ± 736 g; there were no significant foetal malformations in the sample. No significant difference was found in pregnancy or obstetric outcomes between ART-obtained and spontaneous pregnancies. However, the incidence of induction of labour, caesarean section, and post-partum haemorrhage appears higher than in the general population. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of the study may introduce bias, and the sample size might be insufficient for assessing rare obstetric complications. WIDER IMPLICATIONS OF THE FINDINGS: This study offers valuable insights for healthcare providers to guide patients who received fertility-sparing treatments for AH/EC. These pregnancies can be successful and with an acceptable live birth rate, but they seem to be managed with caution, leading to possible tendency for more caesarean sections and labour inductions. No increase in adverse obstetric outcomes was observed, with the exception of suspicion of a higher risk of post-partum haemorrhaging, to be confirmed. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for this study. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.
Assuntos
Cesárea , Neoplasias do Endométrio , Preservação da Fertilidade , Resultado da Gravidez , Humanos , Feminino , Gravidez , Preservação da Fertilidade/métodos , Adulto , Estudos Retrospectivos , Neoplasias do Endométrio/terapia , Neoplasias do Endométrio/complicações , Hiperplasia Endometrial/terapia , Hiperplasia Endometrial/complicações , Nascido Vivo , Taxa de Gravidez , Hemorragia Pós-Parto/epidemiologia , Hemorragia Pós-Parto/etiologia , Hemorragia Pós-Parto/prevenção & controle , França/epidemiologia , Coeficiente de Natalidade , Tratamento Conservador/métodos , Trabalho de Parto Induzido , Técnicas de Reprodução AssistidaRESUMO
Background: Although in vitro fertilization (IVF) in infertile patients with endometrial hyperplasia is common after drug treatment, the pregnancy outcomes are often unsatisfactory. Till date, no studies have reported the outcome of patients with endometrial hyperplasia treated using early-follicular long (EL) protocol and midluteal long (ML) protocol. Objective: To evaluate the pregnancy outcomes and disease prognosis of patients with endometrial hyperplasia with or without atypia undergoing IVF treatment with EL protocol or ML protocol. Methods: This was a retrospective study in university-affiliated reproductive medical center. A total of 138 patients with endometrial hyperplasia undergoing IVF treatment were included to compare the pregnancy outcomes and disease prognosis between EL and ML protocols. We further matched 276 patients with normal endometrium to compare the pregnancy outcomes between patients with endometrial hyperplasia and patients with normal endometrium under different controlled ovarian stimulation (COS) protocol. Results: In patients with endometrial hyperplasia, the clinical pregnancy rate (CPR) and live birth rate (LBR) were significantly higher in EL protocol than in ML protocol (61.8% vs. 43.5%, P=0.032; 50.0% vs. 30.6%, P= 0.022). In the ML protocol, patients with endometrial hyperplasia had significantly lower CPR and LBR than those with normal endometrium (43.5% vs. 59.7%, P=0.037; 30.6% vs. 49.2%, P=0.016). While in the EL protocol, they achieved similar CPR and LBR as patients with normal endometrium (61.8% vs. 69.7%, P=0.232; 50.0% vs. 59.9%, P=0.156). In patients with endometrial hyperplasia, COS protocol was an independent factor affecting clinical pregnancy (adjusted odds ratio [OR] 2.479; 95% confidence interval [CI] 1.154-5.327) and live birth (adjusted OR 2.730; 95% CI 1.249-5.966). After 1-10 years of follow-up, no significant difference was found in the recurrence rate of endometrial lesions between both treatment groups. Conclusions: For patients with endometrial hyperplasia undergoing IVF treatment, the EL protocol is superior to ML protocol, and in the EL protocol, they can achieve similar pregnancy outcomes as patients with normal endometrium.
Assuntos
Hiperplasia Endometrial , Infertilidade , Feminino , Gravidez , Humanos , Hiperplasia Endometrial/complicações , Hiperplasia Endometrial/terapia , Resultado da Gravidez , Estudos Retrospectivos , Fertilização in vitroRESUMO
INTRODUCTION: Our objective was to conduct a systematic review and meta-analysis of studies evaluating the oncological and reproductive outcomes of patients with endometrial atypical hyperplasia (AH) and endometrioid endometrial cancer (EEC) undergoing conservative therapy with hysteroscopic resection (HR). MATERIAL AND METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for systematic reviews and meta-analyses. The study strictly followed the methodological framework proposed by the Cochrane Handbook and was retrospectively registered in PROSPERO (CRD42023469986). Searches were conducted in PubMed, Embase, and the Cochrane Library, from inception to October 10, 2023. A checklist based on items of the Newcastle-Ottawa Scale and the Methodological Index for Non-randomized Studies was used for quality assessment. The primary end points for this meta-analysis were complete response (CR), pregnancy, and live birth rates following HR-based therapy in patients with EEC or AH. The secondary end point was the recurrence rate (RR). RESULTS: Twenty-one articles involving 407 patients with clinical stage IA, low or intermediate grade, EEC, and 444 patients with AH managed with HR-based conservative treatment were included for this systematic review. CR to HR-based conservative therapy was achieved in 88.6% of patients with EEC and 97.0% of patients with AH. Of these, 30.6% and 24.2%, respectively, had live births. The overall pooled disease RR was 18.3% and 10.8% in patients with EEC and AH, respectively. Further subset analyses revealed that EEC patients with body mass index (BMI) ≤28 kg/m2 had higher CR rates as well as higher chances of pregnancy and live birth (91.6% CR, 32.9% pregnancy, 31.1% live birth) compared with patients with BMI >28 kg/m2 (86.4% CR, 28.4% pregnancy, 23.0% live birth). The HR followed by oral progestogen subgroup had higher CR rates and higher chances of pregnancy and live birth (91.8% CR, 36.3% pregnancy, 28.2% live birth) than the HR followed by the levonorgestrel intrauterine system subgroup (82.5% CR, 25.3% pregnancy, 16.3% live birth). CONCLUSIONS: Hysteroscopic resection followed by progestins appears to be a promising choice for fertility-sparing treatment in young patients with AH and EEC, with effective and safe responses. The live birth rate remains to be improved by providing medical guidance and encouragement.
Assuntos
Tratamento Conservador , Hiperplasia Endometrial , Neoplasias do Endométrio , Histeroscopia , Humanos , Feminino , Neoplasias do Endométrio/cirurgia , Neoplasias do Endométrio/terapia , Neoplasias do Endométrio/patologia , Hiperplasia Endometrial/cirurgia , Hiperplasia Endometrial/terapia , Gravidez , Tratamento Conservador/métodos , Taxa de GravidezRESUMO
BACKGROUND: Endometrial hyperplasia (EH) is a precusor lesion for endometrial cancer (EC), the commonest gynaecological malignancy in high-income countries. EH is a proliferation of glandular tissue, classified as either non-atypical endometrial hyperplasia (NEH) or, if the cytological features are abnormal, atypical endometrial hyperplasia (AEH). The clinical significance of AEH is that patients face both a high risk of having occult EC and a high risk of progression to EC if untreated. Recommendations on the care of women with EH were introduced by United Kingdom-wide guidance (Green-top Guide No. 67, 2016). National adherence to guidance is unknown. We aimed to describe the care of patients with EH; to compare the patterns of care for those with EH with national guidance to identify opportunities for quality improvement; and to compare patterns of care prior to and following the introduction of national guidance to understand its impact. METHODS AND FINDINGS: In this UK-wide patient-level clinical audit, we included 3,307 women who received a new histological diagnosis of EH through a gynaecology service between 1 January 2012 and 30 June 2020. We described first-line management, management at 2 years, and surgical characteristics prior to and following national guidance for EH using proportions and 95% confidence intervals (CIs) and compared process measures between time periods using multilevel Poisson regression. Of the 3,307 patients, 1,570 had NEH and 1,511 had AEH between 2012 and 2019. An additional 85 patients had NEH and 141 had AEH during 2020. Prior to national guidance, 9% (95% CI [6%, 15%]) received no initial treatment for NEH compared with 3% (95% CI [1%, 5%]) post-guidance; 31% (95% CI [26%, 36%]) and 48% (95% CI [43% 53%]) received an intrauterine progestogen, respectively, in the same periods. The predominant management of women with AEH did not differ, with 68% (95% CI [61%, 74%]) and 67% (95 CI [63%, 71%]) receiving first-line hysterectomy, respectively. By 2 years, follow-up to histological regression without hysterectomy increased from 38% (95% CI [33%, 43%]) to 52% (95% CI [47%, 58%]) for those with NEH (rate ratio (RR) 1.38, 95% CI [1.18, 1.63] p < 0.001). We observed an increase in the use of total laparoscopic hysterectomy among those with AEH (RR 1.26, 95% CI [1.04, 1.52]). In the later period, 37% (95% CI [29%, 44%]) of women initially diagnosed with AEH who underwent a first-line hysterectomy, received an upgraded diagnosis of EC. Study limitations included retrospective data collection from routine clinical documentation and the inability to comprehensively understand the shared decision-making process where care differed from guidance. CONCLUSIONS: The care of patients with EH has changed in accordance with national guidance. More women received first-line medical management of NEH and were followed up to histological regression. The follow-up of those with AEH who do not undergo hysterectomy must be improved, given their very high risk of coexistent cancer and high risk of developing cancer.
Assuntos
Hiperplasia Endometrial , Neoplasias do Endométrio , Humanos , Feminino , Hiperplasia Endometrial/diagnóstico , Hiperplasia Endometrial/epidemiologia , Hiperplasia Endometrial/terapia , Estudos Retrospectivos , Coleta de Dados , DocumentaçãoRESUMO
OBJECTIVE: This study aimed to investigate the impact of molecular classification and PTEN, KRAS and PIK3CA gene mutation on the outcome of fertility-preserving treatment in the patients with endometrioid endometrial cancer (EEC) and endometrial atypical hyperplasia (EAH). METHODS: This is a single-center retrospective study. A total of 135 patients with EEC and EAH receiving fertility-preserving treatment and molecular classification were reviewed. The distribution of the four types of molecular classification was described. The impact of non-specific molecular profile (NSMP), mismatch repair-deficiency (MMRd), and PTEN, KRAS and PIK3CA gene mutation on the outcome of fertility-preserving treatment was analyzed. RESULTS: Of the patients analyzed, 86.7% (117/136) were classified as having NSMP; 14 (10.4%), MMRd; 1 (0.7%), POLEmut EAH; and 3 (2.2%), p53abn EEC. The patients having NSMP and MMRd achieved similar 16-, 32-, and 48-week complete response rates. The patients harboring tier I and tier II PTEN mutations (PTENmut-Clin) achieved lower cumulative 32-week CR rates than those with PTEN-others (without PTENmut-Clin) (22/47, 46.8% vs. 50/74, 67.6%; p=0.023; odds ratio=0.422; 95% confidence interval [CI]=0.199-0.896). Insulin-resistance (hazard ratio [HR]=0.435; 95% CI=0.269-0.702; p=0.001) and PTENmut-Clin (HR=0.535; 95% CI=0.324-0.885; p=0.015) were independent negative predictors for lower 32-week CR rates. CONCLUSION: PTENmut-Clin is an independent risk factor for unfavorable fertility-preserving treatment outcomes in the patients with EEC and EAH. The patients with MMRd receiving fertility-preserving treatment achieved outcomes similar to those of the patients with NSMP. The molecular profiles might guide fertility-preserving treatment in the prognosis and clinical decisions.
Assuntos
Carcinoma Endometrioide , Hiperplasia Endometrial , Neoplasias do Endométrio , Feminino , Humanos , Neoplasias do Endométrio/terapia , Neoplasias do Endométrio/tratamento farmacológico , Hiperplasia , Estudos Retrospectivos , Proteínas Proto-Oncogênicas p21(ras)/genética , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/terapia , Resultado do Tratamento , Hiperplasia Endometrial/terapia , Hiperplasia Endometrial/tratamento farmacológico , Classe I de Fosfatidilinositol 3-Quinases/genética , Classe I de Fosfatidilinositol 3-Quinases/uso terapêutico , Fertilidade/genética , Mutação , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , PTEN Fosfo-Hidrolase/uso terapêuticoRESUMO
Objectives: Real-world data indicated that some endometrial atypical hyperplasia (EAH) and early endometrial carcinoma (EEC) patients of fertility preservation had a normal ovarian reserve, while some had a decreased ovarian reserve (DOR). This study was designed to investigate the effect of baseline ovarian reserve on the treatment of EAH and EEC patients who ask for preservation of fertility. Methods: This was a prospective cohort study conducted at a single university-affiliated fertility center. A total of 102 EAH and EEC patients who received fertility-preserving treatment between March 2019 and August 2020 were included and divided into a DOR group (n=22) and a non-DOR group (n=80). Results: The 32-week CR rate of the non-DOR group was significantly higher than that of the DOR group (60.3% vs. 33.3%, P =0.028). The DOR group had a longer treatment duration to achieve CR than the non-DOR group (40.07 vs. 29.71 weeks, P=0.008, HR: 0.54, 95% CI: 0.36-0.86). Multivariate logistic regression analyses demonstrated that DOR (OR: 0.35, 95% CI: 0.13-0.99, P=0.049) and BMI ≥25 kg/m2 (OR: 0.40, 95% CI: 0.17-0.92, P=0.031) were negatively associated with 32-week CR. Conclusions: Decreased baseline ovarian reserve is negatively correlated with the efficacy of fertility-preserving treatment in EAH and EEC patients, as this group has a lower CR rate and a longer treatment duration to achieve CR than those without DOR.
Assuntos
Hiperplasia Endometrial , Neoplasias do Endométrio , Reserva Ovariana , Humanos , Feminino , Hiperplasia , Tratamento Conservador , Estudos Prospectivos , Neoplasias do Endométrio/terapia , Hiperplasia Endometrial/terapiaRESUMO
The objectives of this Clinical Expert Series on endometrial hyperplasia are to review the etiology and risk factors, histologic classification and subtypes, malignant progression risks, prevention options, and to outline both surgical and nonsurgical treatment options. Abnormal uterine and postmenopausal bleeding remain the hallmark of endometrial pathology, and up to 10-20% of postmenopausal bleeding will be either hyperplasia or cancer; thus, immediate evaluation of any abnormal bleeding with either tissue procurement for pathology or imaging should be undertaken. Although anyone with a uterus may develop atypical hyperplasia, also known as endometrial intraepithelial neoplasia (EIN), genetic predispositions (eg, Lynch syndrome), obesity, chronic anovulation, and polycystic ovarian syndrome all markedly increase these risks, whereas use of oral contraceptive pills or progesterone-containing intrauterine devices will decrease the risk. An EIN diagnosis carries a high risk of concomitant endometrial cancer or eventual progression to cancer in the absence of treatment. The definitive and curative treatment for EIN remains hysterectomy; however, the obesity epidemic, the potential desire for fertility-sparing treatments, the recognition of varying rates of malignant transformation, medical comorbidities, and an aging population all may factor into decisions to employ nonsurgical treatment modalities.
Assuntos
Carcinoma in Situ , Hiperplasia Endometrial , Neoplasias do Endométrio , Idoso , Feminino , Humanos , Hiperplasia Endometrial/diagnóstico , Hiperplasia Endometrial/etiologia , Hiperplasia Endometrial/terapia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/etiologia , Hiperplasia/complicações , Obesidade/complicações , Obesidade/epidemiologia , Hemorragia Uterina/etiologiaRESUMO
Objective: To investigate the clinical features of obesity indicators in patients with endometrial atypical hyperplasia (EAH) and early endometrial cancer (EC) and analyze the relationship between these indexes and effect of fertility preservation therapy. Methods: The clinical data of patients with EAH, EC and endometrial benign lesions treated in Peking University People's Hospital from January 1, 2018 to June 30, 2021 who required fertility-sparing treatment were collected, and obesity indicators were calculated and analyzed retrospectively. Results: (1) Obesity indicators: the obesity [body mass index (BMI) ≥28 kg/m2] rate of patients with fertility preservation treatment was 40% (32/80), and abdominal obesity [waist circumference (WC) ≥80 cm] rate was 79% (63/80), and obesity indicators [BMI, WC, waist-hip ratio (WHR), weight height ratio (WHTR), body roundness index (BRI), lipid accumulation index (LAP), visceral adiposity index (VAI)] were higher than those with endometrial benign lesions (all P<0.001). (2) Related factors affecting the efficacy of fertility preservation treatment and their predictive value: EC, higher BMI, WC, WHR, WHTR and BRI were risk factors for lower complete remission rate after nine months' treatment (all P<0.05). The predictive values of BRI and WHTR combined with pathological type were superior to other indicators [area under the curve (AUC)=0.716; AUC=0.714]. (3) Relation of obesity indicators and glucolipid indicators:BMI, WC, WHR, WHTR, BRI, LAP and VAI were positively correlated with homeostasis model assessment-insulin resistance index, glycosylated hemoglobin, and triacylglycerol (all P<0.05); while VAI was negatively correlated with high density lipoprotein cholesterol (P<0.001). Conclusions: For patients with EAH and EC treated with fertility preservation therapy, abnormal obesity indexes affect the treatment effect. BRI and WHTR combined pathology have good predictive value for effect of fertility preservation treatment. In clinical practice, appropriate indicators could be selected to evaluate body shape, glucolipid metabolism and predict efficacy.
Assuntos
Hiperplasia Endometrial , Neoplasias do Endométrio , Preservação da Fertilidade , Feminino , Humanos , Hiperplasia , HDL-Colesterol , Hemoglobinas Glicadas , Estudos Retrospectivos , Circunferência da Cintura , Obesidade/complicações , Índice de Massa Corporal , Fatores de Risco , Hiperplasia Endometrial/terapia , Neoplasias do Endométrio/terapia , TriglicerídeosRESUMO
RESEARCH QUESTION: Do IVF treatments after conservative management of endometrial atypical hyperplasia or grade 1 endometrial adenocarcinoma (AH/EC) increase the risk of disease recurrence? DESIGN: This is a prospective cohort study from a national registry from January 2008 to July 2019. Sixty patients had an AH/EC and received progestin treatment using chlormadinone acetate for at least 3 months. After remission, 31 patients underwent IVF and 29 did not. The primary outcome was the recurrence rate at 24 months according to the use of IVF. The secondary outcome was the identification of risk factors for recurrence. RESULTS: The probability of 2-year recurrence was 37.7% (SD 10.41%) in the IVF group and 55.7% (SD 14.02%) in the no IVF group (Pâ¯=â¯0.13). Obesity, nulliparity, polycystic ovary syndrome, age and tumoural characteristics were not associated with recurrence. Pregnancy was a protective factor for recurrence, with 2-year recurrence probabilities of 20.5% and 62.0% in the pregnancy and no pregnancy groups, respectively (Pâ¯=â¯0.002, 95% CI 0.06-0.61). In contrast, the number of cycles, maximum serum oestradiol concentration during ovarian stimulation, ovarian stimulation protocol, total dose of gonadotrophin administered and thickness of the endometrium showed no significant differences in terms of the risk of recurrence in the IVF subgroup. CONCLUSION: IVF treatment after fertility-sparing management of AH/EC does not increase the risk of recurrence. Therefore, it is an acceptable strategy to decrease the time to pregnancy. Overall, the recurrence rate is high enough to justify close monitoring once remission occurs.
Assuntos
Adenocarcinoma/terapia , Neoplasias do Endométrio/terapia , Preservação da Fertilidade , Fertilização in vitro , Recidiva Local de Neoplasia/etiologia , Tratamentos com Preservação do Órgão , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Adulto , Estudos de Coortes , Tratamento Conservador/efeitos adversos , Tratamento Conservador/estatística & dados numéricos , Hiperplasia Endometrial/epidemiologia , Hiperplasia Endometrial/patologia , Hiperplasia Endometrial/terapia , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/patologia , Feminino , Fertilidade/fisiologia , Preservação da Fertilidade/efeitos adversos , Preservação da Fertilidade/métodos , Preservação da Fertilidade/estatística & dados numéricos , Fertilização in vitro/efeitos adversos , Fertilização in vitro/estatística & dados numéricos , França/epidemiologia , Humanos , Incidência , Recidiva Local de Neoplasia/epidemiologia , Tratamentos com Preservação do Órgão/efeitos adversos , Tratamentos com Preservação do Órgão/estatística & dados numéricos , Gravidez , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
Adult stem cells (ASCs) were long suspected to exist in the endometrium. Indeed, several types of endometrial ASCs were identified in rodents and humans through diverse isolation and characterization techniques. Putative stromal and epithelial stem cell niches were identified in murine models using label-retention techniques. In humans, functional methods (clonogenicity, long-term culture, and multi-lineage differentiation assays) and stem cell markers (CD146, SUSD2/W5C5, LGR5, NTPDase2, SSEA-1, or N-cadherin) facilitated the identification of three main types of endogenous endometrial ASCs: stromal, epithelial progenitor, and endothelial stem cells. Further, exogenous populations of stem cells derived from bone marrow may act as key effectors of the endometrial ASC niche. These findings are promoting the development of stem cell therapies for endometrial pathologies, with an evolution towards paracrine approaches. At the same time, promising therapeutic alternatives based on bioengineering have been proposed.
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Adenomiose/terapia , Células-Tronco Adultas/citologia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Hiperplasia Endometrial/terapia , Neoplasias do Endométrio/terapia , Endometriose/terapia , Leiomioma/terapia , Adenomiose/metabolismo , Adenomiose/patologia , Células-Tronco Adultas/metabolismo , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Diferenciação Celular , Linhagem da Célula/genética , Hiperplasia Endometrial/metabolismo , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Endometriose/metabolismo , Endometriose/patologia , Endométrio/citologia , Endométrio/metabolismo , Feminino , Humanos , Leiomioma/metabolismo , Leiomioma/patologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Comunicação Parácrina , Nicho de Células-Tronco/genéticaAssuntos
Antineoplásicos Hormonais/uso terapêutico , Carcinoma Endometrioide/terapia , Hiperplasia Endometrial/terapia , Neoplasias do Endométrio/terapia , Histeroscopia , Acetato de Megestrol/uso terapêutico , Aborto Espontâneo , Carcinoma Endometrioide/patologia , Terapia Combinada , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/patologia , Feminino , Preservação da Fertilidade/métodos , Fertilização in vitro/estatística & dados numéricos , Humanos , Nascido Vivo , Gravidez , Taxa de Gravidez , Prognóstico , Estudos ProspectivosRESUMO
Purpose: Predictive markers of response to conservative treatment of atypical endometrial hyperplasia (AEH) or early endometrial cancer (EEC) are still lacking. We aimed to assess clinical predictive factors of response to conservative treatment of AEH and EEC. Methods: All patients with AEH or EEC conservatively treated from January 2007 to June 2018 were retrospectively assessed. The associations between 23 clinical factors and outcomes of response to treatment were assessed with standard univariate analyses and multivariate logistic regression (significant p-value <0.05). The primary outcome was the association of each clinical factor with treatment failure (i.e., no regression or relapse of the disease). Secondary outcomes were the associations of each clinical factor with: (1) no regression, (2) relapse, or (3) pregnancy after treatment. Results: Forty-three women, 37 (86%) with AEH and 6 (14%) with EEC were included. At univariate analyses, treatment failure was associated with longer menstrual cycle (p = 0.002), infrequent menstrual bleeding (p = 0.04), and a diagnosis of EEC instead of AEH (p = 0.008). Among the secondary outcomes, no regression was associated with infrequent menstrual bleeding (p = 0.04), and a diagnosis of EEC instead of AEH (p < 0.001), while relapse was associated with longer menstrual cycles (p = 0.007). At multivariate analyses, odds ratio for treatment failure was 4.54 (95% confidence interval [CI], 0.24-84.4) for a diagnosis of EEC instead of AEH (p = 0.3), and 2.10 (95% CI, 1.03-4.29) for longer menstrual cycles (p = 0.042), while infrequent menstrual bleeding perfectly predicted treatment failure. Conclusions: Longer menstrual cycles and infrequent menstrual bleeding appear as independent predictive factors for conservative treatment failure in AEH and EEC. Further and larger studies are necessary to confirm these findings.
Assuntos
Hiperplasia Endometrial , Neoplasias do Endométrio , Tratamento Conservador , Hiperplasia Endometrial/terapia , Neoplasias do Endométrio/terapia , Feminino , Humanos , Recidiva Local de Neoplasia , Gravidez , Estudos RetrospectivosRESUMO
INTRODUCTION: Primary surgery is effective in low-risk endometrial cancer (EC). However, in young women, this approach compromises fertility. Therefore, fertility-sparing management in the case of atypical endometrial hyperplasia, or grade 1 EC limited to the endometrium can be considered. EVIDENCE ACQUISITION: We performed a literature review to identify studies involving women with EC or atypical hyperplasia who underwent fertility-sparing management. We conducted multiple bibliographic databases research from their inception to May 2020. EVIDENCE SYNTHESIS: Oral therapy with medroxyprogesterone acetate and megestrol acetate is recommended based on extensive experience, although without consensus on dosages and treatment length. The pooled complete response rate, recurrence rate, and pregnancy rate of EC were 76.3%, 30.7% and 52.1%, respectively. Endometrial hyperplasia was associated with better outcomes. LNG-IUSs appears an alternative treatment, particularly in patients who do not tolerate oral therapy. In a randomized controlled trial, megestrol acetate plus metformin guaranteed an earlier complete response rate than megestrol acetate alone for endometrial hyperplasia. Hysteroscopic resection followed by progestogens is associated with a higher complete response rate, live birth rate, and lower recurrence rate than oral progestogens alone. Pooled complete response, recurrence, and live birth rates were 98.1%, 4.8% and 52.6%. CONCLUSIONS: Fertility preservation appears feasible in young patients with grade 1 EC limited to the endometrium or atypical endometrial hyperplasia. Progestins are the mainstay of such management. The addition of Metformin and hysteroscopic resection seems to provide some improvements. However, fertility preservation is not the standard approach for staging and treatment, potentially worsening oncologic outcomes.
Assuntos
Hiperplasia Endometrial/terapia , Neoplasias do Endométrio/terapia , Preservação da Fertilidade/métodos , Administração Oral , Portadores de Fármacos , Feminino , Humanos , Histeroscopia , Levanogestrel/administração & dosagem , Metformina/uso terapêutico , Progestinas/administração & dosagemRESUMO
OBJECTIVE: To describe knowledge and attitudes toward fertility preservation (FP) in patients with endometrial atypical hyperplasia or adenocarcinoma (EC/AH) among French gynecologists MATERIALS AND METHODS: A national survey among French gynaecologists: one questionnaire with one common part and two specific parts for gynecological surgeon (GS) or for specialists in reproductive medicine (SRM) was sent from April 2017 to April 2018. Knowledge and attitudes toward FP in EC/AH were evaluated with a "knowledge score" and an "attitudes score" using a four- or five-point Likert scale. RESULTS: One hundred forty physicians completed the survey (87 GS, 53 SRM). The knowledge score was low (59.3% medium/low), but it was significantly higher for GS compared to SRM. The better-known treatments were oral progestins and hysteroscopic resection. Among the participants treating EC/AH, 52.6% found it "difficult" to manage patients and 61.8% regretted the lack of official recommendations. Most physicians seemed to be uncomfortable/unsupportive with FP in EC/AH (57.2% "attitude score' below 11/20). There was a positive correlation between knowledge and attitude scores. GS "usually/always" give advice to patients about FP before EC/AH treatment. After maximum 3-6 months, 56.6% of SRM chose In Vitro Fecundation (IVF) to reduce time-to-pregnancy, with GnRH antagonist protocols (28%) or mild-stimulation (15.1%) to avoid hyperoestrogenism. CONCLUSIONS: Despite reassuring results in the literature, French gynecologists are uncomfortable with FP using EC/AH conservative management, which may be because of a lack of confidence in their knowledge. Specific guidelines are needed to help physicians manage these young patients and their fertility.
Assuntos
Tratamento Conservador/métodos , Neoplasias do Endométrio/terapia , Preservação da Fertilidade/métodos , Ginecologia/métodos , Conhecimentos, Atitudes e Prática em Saúde , Medicina Reprodutiva/métodos , Adenocarcinoma/terapia , Adulto , Atitude do Pessoal de Saúde , Hiperplasia Endometrial/terapia , Neoplasias do Endométrio/cirurgia , Feminino , França , Hormônio Liberador de Gonadotropina/agonistas , Procedimentos Cirúrgicos em Ginecologia/métodos , Humanos , Histeroscopia , Dispositivos Intrauterinos Medicados , Levanogestrel/administração & dosagem , Levanogestrel/uso terapêutico , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Gravidez , Progestinas/uso terapêutico , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: The purpose of this study was to define the pregnancy and oncologic outcomes after fertility-sparing treatment of atypical hyperplasia (AH)/endometrial intraepithelial neoplasia (EIN) and early-stage endometrioid endometrial cancer (EEC). MATERIALS AND METHODS: The retrospective cohort study included patients who had applied to Baskent University's Ankara Hospital between January 2007 and October 2018 with either AH/EIN (n: 27; Group A) or EEC (n: 30; Group B), and who had the desire to preserve their fertility. The medical records of all patients included in the study were reviewed retrospectively from the hospital records. RESULTS: There were 2 (7.4%) and 5 (16.7%) recurrences, whereby one patient from Group A and two patients from Group B underwent staging surgery. In Group A, 8 patients attempted pregnancy after their treatment and 4 of them (50%) became pregnant, while 3 of them (37.5%) had a live birth. In Group B, there were 17 patients who wanted to become pregnant following treatment of the disease; 8 of them (47%) became pregnant after treatment, 5 of them (16.6%) had a live birth, 1 experienced intrauterine exitus (at 21st gestational week, 350 g), and 2 currently have ongoing pregnancies. CONCLUSION: Hysteroscopic resection of visible lesions and full endometrial curettage prior to hormonal therapy as a fertility-preserving approach for women of reproductive age with endometrial malignancies can achieve promising oncologic and obstetric responses.
Assuntos
Carcinoma in Situ/terapia , Hiperplasia Endometrial/terapia , Neoplasias do Endométrio/terapia , Preservação da Fertilidade/métodos , Histeroscopia/métodos , Adulto , Antineoplásicos Hormonais/efeitos adversos , Carcinoma in Situ/patologia , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Infertilidade Feminina/induzido quimicamente , Infertilidade Feminina/prevenção & controle , Estadiamento de Neoplasias , Lesões Pré-Cancerosas , Gravidez , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Objective: To analyze the clinical efficacy and pregnancy outcomes of fertility- preserving re-treatment in patients with recurrent atypical endometrial hyperplasia (AEH) and early stage endometrial carcinoma (EEC) after achieved complete remission (CR) of primary fertility-preserving therapy. Methods: There were 104 cases of AEH and EEC collected from 9 hospitals in the multi-center research network platform of fertility-preserving therapy of endometrial carcinoma in China from January 2005 to May 2019. Thirth-one cases of them relapsed from four hospitals mentioned above,who achieved CR after primary fertility-preserving therapy,was analyzed retrospectively. Of the 31 cases, 27 cases chose fertility-preserving re-treatment. The demographic characteristics, re-treatment effect, clinical factors and pregnancy outcomes were observed. Results: (1) There were 16 AEH cases and 11 ECC cases among 27 recurrent patients who chose fertility-preserving therapy again. After re-treatment, CR was found in 13 out of 16 cases of AEH and 9 out of 11 cases of EEC. The overall CR rate was 81% (22/27). (2) After CR of recurrence, 5 cases (23%, 5/22) of re-recurrence were found after with a median time of 33 months (range 21-80 months). There were 4 cases underwent comprehensive surgical staging, and 1 patient chose the third round of fertility preservation therapy with fully informed consent, and CR was reached after 15 months. (3) There were 16 cases with pregnancy intention, with a total of 12 pregnancies, including 5 cases were natural pregnancy and 7 cases were assisted reproductive technology pregnancy. There were 5 live births. The follow-up time was up to May 2019, and the median follow-up time was 73 months (range 0-123 months). All 27 patients had disease free survival. Conclusions: Recurrent patients with AEH and EEC after achieving successful fertility-preserving therapy could choose fertility-preserving therapy again with comprehensive assessment and fully informed consent. After re-treatment, there is a certain tumor CR rate and pregnancy rate, while the close follow-up is required during treatment.
Assuntos
Carcinoma/terapia , Hiperplasia Endometrial/terapia , Neoplasias do Endométrio/terapia , Preservação da Fertilidade , China , Feminino , Humanos , Recidiva Local de Neoplasia , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of the study was to review the management of endometrial hyperplasia in a woman undergoing liver transplantation for alcoholic cirrhosis. METHODS: This is a case presentation on a postmenopausal woman with a tissue diagnosis of endometrial intraepithelial neoplasia managed with a levonorgestrel intrauterine device, before and after liver transplantation. Full written informed consent was obtained from the patient to present her case. RESULTS: The patient experienced resolution of her endometrial intraepithelial neoplasia with conversion to atrophic endometrium after management with levonorgestrel intrauterine device. CONCLUSIONS: A large percentage of women with cirrhosis experience abnormal uterine bleeding, which may be due to the coagulopathy that accompanies liver disease, or endometrial hyperplasia or carcinoma. Although hysterectomy is the criterion standard of treatment for atypical endometrial hyperplasia in a postmenopausal woman, patients with cirrhosis severe enough to require transplant are usually poor surgical candidates. Multiple studies have shown success with conservative management of atypical hyperplasia. There is a paucity of literature on managing patients undergoing transplant with abnormal uterine bleeding and it is therefore important to highlight conservative management options for this patient population.