Pregnancy and obstetric outcomes after fertility-sparing management of endometrial cancer and atypical hyperplasia: a multicentre cohort study.

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.

Pregnancy outcomes in infertile patients with endometrial hyperplasia with or without atypia undergoing in vitro fertilization: the early-follicular long protocol is superior to midluteal long protocol.

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.

Diagnostic significance and predictive efficiency of metabolic risk score for fertility-sparing treatment in patients with atypical endometrial hyperplasia and early endometrial carcinoma.

OBJECTIVE: This study aims to assess the impact of the metabolic risk score (MRS) on time to achieve complete remission (CR) of fertility-sparing treatments for atypical endometrial hyperplasia (AEH) and early endometrial cancer (EC) patients. METHODS: Univariate and multivariate cox analyses were employed to identify independent risk factors affecting the time to CR with patients at our center. These factors were subsequently incorporated into receiver operator characteristic curve analysis and decision curve analysis to assess the predictive accuracy of time to CR. Additionally, Kaplan-Meier analysis was utilized to determine the cumulative CR rate for patients. RESULTS: The 173 patients who achieved CR following fertility preservation treatment (FPT) were categorized into three subgroups based on their time to CR (<6, 6-9, >9 months). Body mass index (hazard ratio [HR]=0.20; 95% confidence interval [CI]=0.03, 0.38; p=0.026), MRS (HR=0.31; 95% CI=0.09, 0.52; p=0.005), insulin resistance (HR=1.83; 95% CI=0.05, 3.60; p=0.045), menstruation regularity (HR=3.77; 95% CI=1.91, 5.64; p=0.001), polycystic ovary syndrome (HR=-2.16; 95% CI=-4.03, -0.28; p=0.025), and histological type (HR=0.36; 95% CI=0.10, 0.62; p=0.005) were identified as risk factors for time to CR, with MRS being the independent risk factor (HR=0.29; 95% CI=0.02, 0.56; p=0.021). The inclusion of MRS significantly enhanced the predictive accuracy of time to CR (area under the curve [AUC]=0.789 for Model 1, AUC=0.862 for Model 2, p=0.032). Kaplan-Meier survival curves revealed significant differences in the cumulative CR rate among different risk groups. CONCLUSION: MRS emerges as a novel evaluation system that substantially enhances the predictive accuracy for the time to achieve CR in AEH and early EC patients seeking fertility preservation.

Predicting Endometrial Hyperplasia and Endometrial Cancer on Recurrent Abnormal Uterine Bleeding.

OBJECTIVE: To develop predictive models for endometrial hyperplasia and endometrial cancer in patients with recurrent abnormal uterine bleeding (AUB). METHODS: This retrospective cohort study analyzed patients with recurrent AUB who had previous endometrial sampling that showed benign results between January 2013 and December 2021. A model was constructed from the significant factors associated with endometrial hyperplasia and endometrial cancer using multivariate logistic regression. Risk scores were calculated from the log odds of each significant predictive factor and were subsequently subcategorized into risk groups. The overall performance and internal validation of the model were assessed with the area under the receiver operating characteristic curve (AUC) and bootstrap methods. RESULTS: Of the total 456 patients with recurrent AUB, endometrial hyperplasia and endometrial cancer were detected in 8.3% and 2.2% of cases, respectively. The average interval between the first and second endometrial samplings was 25.1 months. Factors significantly associated with endometrial hyperplasia and endometrial cancer included age older than 45 years (odds ratio [OR] 2.86, 95% CI, 1.31-7.03), nulliparity (OR 3.50, 95% CI, 1.76-6.85), a history of endometrial polyp (OR 3.69, 95% CI, 1.93-7.05), and an interval of less than 12 months between sampling (OR 2.36, 95% CI, 1.25-4.42). Predictive factors were scored and categorized into three groups: 0-3, 5-8, and 9-11 points. The corresponding risks for endometrial hyperplasia and endometrial cancer in these groups were 4.7%, 15.5%, and 57.1%, respectively. The AUC was 73.1%, with a mean absolute error of 0.01. CONCLUSION: Endometrial hyperplasia and endometrial cancer occur at low incidence among one-fifth of patients with AUB who experience recurrent bleeding. Older age, nulliparity, a history of endometrial polyps, and an interval of less than 12 months between samplings are predictive factors for endometrial hyperplasia and endometrial cancer in this cohort.

Sangrado y terapia hormonal en la menopausia (THM) / Bleeding during menopause hormone therapy (MHT)

La definición de sangrado ginecológico anormal durante terapia hormonal de la menopausia es aquel sangrado no programado durante el uso de la terapia. Este artículo es un pauteo que describe: 1) cuándo diagnosticar unsangrado anormal, ya que difiere según el tipo de esquema hormonal utilizado; 2) eldiagnóstico diferencial del origen del sangrado anormal; 3) los métodos de evaluación para diagnosticar el origen del sangrado. Se destacan los aspectos principales para el diagnóstico diferencial entre patología orgánica versus disrupción endometrial debida al tratamiento hormonal. Además, se describen los ajustes posibles para resolver el sangrado cuando éste se debe a disrupción del endometrio.

Abnormal bleeding related to menopausal hormone therapy is defined as unscheduled bleeding during the use of the therapy. This article outlines when to diagnose an abnormal bleeding -as this differs according to the type of hormonal scheme used-, the differential diagnosis of the origin of abnormal bleeding, and the methods of evaluation to assess the origin of the bleeding. The main aspects are highlighted on the differentiation of organic pathology versus disruption of the endometrium due to treatment. Also, treatment adjustments to resolve bleeding when it is due to disruption of the endometrium are outlined.

Nódulo o placa de sitio placentario / Nodule or plaque of placental site

Se presenta el primer caso en nuestro medio de Nodulo placentario con la idea de que se reconozca histologicamente y que se diferencie de otras condiciones, para el manejo adecuado de los pacientes, dado que la condicion es poco conocida y solo hay reportados 20 casos en la literatura americana

Sangramento na pós menopausa: avaliaçäo clínica e histopatológica / Clinical and hystopatological findings in women with postmenopausal bleeding

OBJETIVO: Avaliaçäo clínica e análise histopatológica do endométrio em pacientes com sangramento na pós-menopausa. PACIENTES E MÉTODOS: Foram analisadas, retrospectivamente, 268 pacientes com sangramento uterino na pós-menopausa, submetidas e curetagem uterina diagnóstica. De acordo com o achado histopatológico, foram separadas as pacientes com lesöes endometriais benignas, pré-malignas e malignas. RESULTADOS: A análise histopatológica mostrou que 79,1 por cento destas mulheres apresentam lesöes endometriais benignas e 20,9 por cento pré-malignas e malignas, correspondendo a hiperplasia atípica e adenocarcinoma de endométrio. Endométrio atrófico (28,7 por cento) foi o achado endometrial mais freqüentemente associado ao sangramento na pós-menopausa, seguido de material insuficiente (18,3 por cento), pólipo endometrial (17,2 por cento), adenocarcinoma (16,4 por cento), hiperplasia sem atipia (10,4 por cento), com atipia (4,5 por cento), proliferativo (3,3 por cento), endometrite (0,4 por cento), secretor (0,4 por cento). Verificou-se que a média de idade das pacientes com hiperplasia atípica e adenocarcinoma foi de 63,2ñ9,6 anos contra 58,5ñ8,0 anos daquelas com lesöes endometriais benignas. A obesidade, diabetes mellitus, hipertensäo arterial, nuliparidade, menopausa tardia e ciclos anovulatórios ocorreram respectivamente, na freqüencia de 49,0 por cento, 16,6 por cento, 49,8 por cento, 6,8 por cento, 25,9 por cento e 11,8 por cento nas lesöes benignas e 39,6 por cento, 33,9 por cento, 58,9 por cento, 28,5 por cento, 32,1 por cento e 12,9 por cento nas pré-malignas e malignas, sendo que a idade, nuliparidade e o diabetes mellitus apresentaram diferença estatisticamente significativa (p<0,05). CONCLUSÕES: O sangramento pós menopausa representa sinal de alerta, necessitando de avaliaçäo histopatológica do endométrio mesmo nas pacientes näo consideradas de risco para o desenvolvimento de câncer de endométrio

Adenomiose: variaçöes do quadro clínico e associaçäo a outras patologias ginecológicas / Adenomiosis: variation in clinical feature and association with other gynecological pathologies

Diante do quadro clínico näo-caracterfstico e da dificuldade do diagnóstico pré-operatório de adenomiose, o objetivo deste estudo foi avaliar os vários parâmetros clínicos encontrados em pacientes, que tiveram o diagnóstico de adenomiose comprovado através de estudo anatomopatológico da peça cirúrgica pós-histerectomia. A adenomiose esteve presente em 118 das 717 histerectomias, realizadas no Hospital das Clínicas da FMRP-USP, durante o período de 1983 a 1986. O diagnóstico pré-operatório foi feito em apenas 15,3 por cento dos casos. A maioria das pacientes era constituída de multíparas na pré-menopausa e apresentavam sangramento uterino anormal e/ou dor pélvica. A adenomiose estava associada a outras patologias pélvicas em 75 pacientes (63,6 por cento), sendo a mais freqüente o leiomioma, seguida de endometriose, hiperplasia do endométrio e pólipo endometrial. A freqüente associaçäo com patologias pélvicas mais comuns, que ela própria e de quadro-clínico semelhante, dificulta o diagnóstico de adenomiose, que, assim, perde a importância clínica, frente a maior exuberância do quadro clínico da entidade mórbida associada.

Perspectivas de manejo en la hiperplasia endometrial. Informe preliminar / The outlook for the management of endometrial hyperplasia. a preliminary report

Con el propósito de encontrar un tratamiento menos traumático y unificar criterios en nuestro medio en el menejo de la Hiperplasia Endometrial (HE) realizamos una prueba farmacológica en siete mujeres con HE y hemorragia uterina en edad fértil (n=3) y perimenopaútisicas (n=4). Se les prescribió noretindrona (NET) 5 mg/45d. No se observaron efectos colaterales indesables. Las siete pacientes mostraron regresión endometrial, dos de las tres jóvenes lograron embarazo a término y las cuatro perimenopaúsicas no volvieron a menstruar. En estas observaciones preliminares no hubo ningún fenómeno de asociación entre hormonas esteroides gonadales (Estradiol E-2, estrona E-1, Progesterona P-4) con la histología endometrial

Lesiones premalignas del endometrio / Endometrium pre-malignant injuries

Se presenta el estudio de 550 pacientes mayores de 30 años, portadores de patología endometrial que fueron sometidas a Biopsia de Endometrio entre los años 1981 a 1985. Los hallazgos histopatológico de endometrios hiperplásicos se encuentran notoriamente agrupados en los grupos de edad correspondiente a pacientes por encima de los 30 años, destacando las hiperplasias quísticas glandulares y iatrogénicas. La hiperplasia adenomatosa tiene una mayor concentración de casos en los grupos etáreos de 40 a 59 años (77.77 por ciento). El 5.92 por ciento cursaron metrorragia y presentaron hiperplasias quísticas. El 3.95 por ciento con el mismo síntoma, tuvieron hiperplasias glándulo-quísticas. El 3.16 por ciento de mujeres con metrorragia, el estudio histopatógico reveló hiperplasia adenomatosa. Cuando el síntoma principal fue menorragia, el hallazgo histopatológico mayor fue el de hiperplasia endometrial simple, quística o iatrogénica (48 por 100) e hiperplasia adenomatosa sólo en 1.34 por 100. En pacientes cuyo síntoma principal fue oligomenorrea, el hallazgo histopatológico arrojó endometrio de tipo proliferativo (18.25 por 100) e hiperplásicos (18.25 por 100).El 53.49 por 100 de pacientes con amenorrea tuvieron endometrios de tipo proliferativo e hiperplásicos. El síntoma metrorragia se asocia preferentemente con adenocarcinoma y pólipo endometrial. La menorragia es síntoma principal de endometrios hiperplásicos adenomatosos, en pacientes por encima de 45 años. En mujeres mayores de 40 años que cursaron con metrorragia, el hallazgo histopatológico fue en el 66 por 100 de endometrios de tipo proliferativo