Assisted reproductive technologies in conjunction with conservatively treated endometrial adenocarcinoma. A case report

This case report illustrates the successful use of assisted reproductive technologies (ARTs) in a patient receiving conservative treatment for endometrial adenocarcinoma. A 31-year-old infertile woman, diagnosed as FIGO stage Ia endometrial adenocarcinoma (grade 1), received oral medroxyprogesterone acetate 400 mg/day for 12 weeks. Endometrial curettage was performed and the absence of endometrial carcinoma was confirmed. A single pregnancy was achieved with in vitro fertilization and embryo transfer. A healthy female infant was born via cesarean section at 42 weeks' gestation. The carcinoma has not recurred, and the patient now desires a second child. We conclude that ART combined with progesterone treatment might be a powerful option for the treatment of infertile patients with early stage, well-differentiated endometrial adenocarcinoma.     

Lymphvascular space involvement—a prognostic indicator in patients with surgical stage I endometrial adenocarcinoma treated with postoperative radiation

The objective of this study was to evaluate the prognostic indices of lymphvascular space involvement (LVS), surgical substage and grade on recurrence and survival in patients with surgical stage I endometrial adenocarcinoma, who had received postoperative external beam radiation (ERT). The medical records of all patients who had surgical stage I endometrial cancer between January 1987 and December 1991 were reviewed. Prognostic indicators, ie LVS, surgical substage and grade were correlated with recurrence and survival by log-rank test. Recurrence and survival distributions were estimated using the product limit method. One hundred and twenty-two patients had surgical stage I endometrial cancer. Eight patients were excluded because of histologic types other than endometrioid adenocarcinoma. An additional 27 patients were excluded since they had surgical stage IA and grade I and had not received ERT. The remaining 87 patients who had surgical stage IB and IC and who had received ERT, are the focus of this study. Ten patients had recurrences, all of which were outside the prescribed field of radiation. Nine of II (82%) patients with LVS recurred and 8/11 (73%) patients with LVS died of disease ( P = 0.0001). Surgical substage did not correlate with risk for recurrence ( P < 0.51). Five-year survival for the study group was 92%. LVS correlated well with survival ( P < 0.0001), while grade and surgical substage were not significant indicators of survival in these patients, with surgically documented early disease ( P > 0.13 and P > 0.57). LVS appears to be an important prognostic indicator for both recurrence and survival in patients with surgical stage I endometrial adenocarcinoma who receive postoperative ERT.     

Pregnancy after in vitro fertilization in a patient with stage I endometrial carcinoma treated with progestins

A 35-year-old woman with chronic anovulation and bilateral tubal disease was found during infertility evaluation to have grade I endometrial carcinoma confined to an endometrial polyp. She was treated with polypectomy and endometrial curettage followed by high-dose progestagens for 6 months. Endometrial curettage at 3 and 6 months of therapy indicated regression of the lesion and the patient subsequently achieved successful pregnancy with IVF.     

A successful pregnancy after intracytoplasmic sperm injection and embryo transfer in a patient with endometrial cancer who was treated conservatively

OBJECTIVE: To describe a patient with polycystic ovary syndrome (PCOS) conceiving with intracytoplasmic sperm injection (ICSI) and embryo transfer after conservative treatment of early stage endometrial cancer. DESIGN: Case report. SETTING: Tertiary center for assisted reproductive technologies.A 32-year-old woman with PCOS, primary infertility of 4 years duration, and grade 1 endometrioid endometrial cancer. INTERVENTION(S): Assessment of myometrial invasion and extrauterine spread with magnetic resonance imaging (MRI) and explorative laparotomy. High-dose progestin treatment and ICSI and embryo transfer. MAIN OUTCOME MEASURE(S): Successful take-home baby and no residual endometrial cancer. RESULT(S): A healthy normal female infant with a birth weight of 1740 g was born by cesarean section at 30 weeks' gestation. No residual cancer was detected at the follow-up curettage performed 2 months after the delivery. CONCLUSION(S): Conservative uterus-preserving treatment may be considered in patients with early stage endometrial cancer. Assisted reproductive technologies may be used in such patients for immediate achievement of pregnancy.     

Long-term effect of megestrol acetate in the treatment of endometrial hyperplasia

Fifty-two postmenopausal women who were poor surgical risks and had histologically proved adenomatous hyperplasia, atypical hyperplasia, or adenocarcinoma in situ of the endometrium were treated with megestrol acetate, 40 mg per day, continuously for 9 to 104 months (mean, 42 months). More than 90% of these women had complete remissions of the hyperplasia. Three women with carcinoma in situ were followed up for 57, 65, and 104 months, without recurrence of the disease. Four women required hysterectomy; none had invasive adenocarcinoma. No adverse side effects of the drug were observed. Thus, we conclude that the continuous use of megestrol acetate is an effective, safe, alternative form of therapy for endometrial hyperplasia in postmenopausal women.     

Pregnancy induced with menotropins in a woman with polycystic ovaries, endometrial hyperplasia, and adenocarcinoma

A 31-year-old woman is described with PCOD associated with endometrial hyperplasia and well-differentiated adenocarcinoma. Conservative treatment with ovulation induction was pursued for a total of 3 1/2 years. After CC treatment failed to achieve conception, treatment with menotropins resulted in a twin pregnancy that aborted spontaneously and a singleton term pregnancy. Hysterectomy was performed 4 1/2 years after the initial diagnosis of well-differentiated endometrial adenocarcinoma was made. Histologic examination of the endometrium showed no progression of the disease. Ovulation induction of patients with polycystic ovaries and well-differentiated and noninvasive endometrial adenocarcinoma may be justified in properly selected cases.     

Treatment of recurrent and metastatic endometrial cancer with cisplatin, doxorubicin, cyclophosphamide, and megestrol acetate

The combination of cisplatin, doxorubicin, cyclophosphamide, and megestrol acetate was used to treat 15 patients with recurrent and metastatic endometrial cancer. Four patients had a complete response and one patient had a partial response, yielding a total response rate of 33%. Five patients had stable disease. The median survival for the whole group was 38 weeks. The median survival for responders was 60 weeks, and that for nonresponders was 21 weeks. The median progression-free survival for the whole group was 17 weeks. The median progression-free survival for responders was 32 weeks, and that for patients with stable disease was 25 weeks. The toxic reactions noted were primarily nausea, vomiting, and myelosuppression. The combination of cisplatin, doxorubicin, cyclophosphamide, and megestrol acetate has modest effectiveness in the treatment of metastatic or recurrent carcinoma of the endometrium.     

Pre-operative magnetic resonance imaging of stage 1 endometrial adenocarcinoma

Twelve women with stage I endometrial adenocarcinoma were examined by magnetic resonance imaging before definitive surgery. Using this technique the depth of myometrical invasion, tumour site and cervical involvement were assessed and the results compared with the operative and pathological findings. Magnetic resonance imaging is a unique non-invasive method of assessing the early stages of endometrial adenocarcinoma before radiotherapy and surgery.     

Successful pregnancy in a patient with endometrial carcinoma treated with medroxyprogesterone acetate

A 32-year infertile Japanese woman suffered from endometrial cancer, which was treated with repeated endometrial curettage and medroxyprogesterone acetate for 6 months. The patient then became pregnant and was delivered of a live-born male infant at 37 weeks gestation by cesarean section for placenta previa. At cesarean section there were no abnormal findings in the uterine cavity or other pelvic organs.     

Two successful pregnancies after in vitro fertilization and embryo transfer in a patient with endometrial atypical hyperplasia bordering on adenocarcinoma treated conservatively with high-dose progesterone

Women suffering from anovulatory infertility may develop endometrial hyperplasia and adenocarcinoma due to the unopposed estrogen effect. We present the case of a young infertile woman with endometrial atypical hyperplasia bordering on adenocarcinoma who refused hysterectomy and bilateral salpingo-oophorectomy and achieved two successful pregnancies after conservative treatment with high-dose progesterone followed by in vitro fertilization and embryo transfer. It is concluded that conservative treatment with high-dose progesterone for endometrial hyperplasia and well-differentiated early-stage adenocarcinoma followed by assisted reproductive technologies is an appropriate means for achieving pregnancy. However, the issue of hysterectomy and bilateral salpingo-oophorectomy after delivery or after fertility being no longer required is controversial. If surgery is not performed, close observation with endometrial sampling every 6 months is advisable.     

Metabolic effects associated with high-dose continuous megestrol acetate administration in the treatment of endometrial pathology

OBJECTIVES: To determine the metabolic effects and efficacy of high-dose continuous megestrol acetate administration in the treatment of endometrial pathology. MATERIAL AND METHODS: 27 women with histologically proven endometrial pathology (endometrial hyperplasia and irregularly proliferative endometrium) were treated with megestrol acetate orally 160 mg/d given once-a-day for 3 months. In 5 of 27 patients the dose of megestrol acetate was increased to 320 mg/d to alleviate irregular uterine bleeding. Serum lipid profiles and fasting and 2-h postprandial serum glucose levels were studied at baseline and one week after the therapy was completed. RESULTS: HDL-cholesterol level significantly lowered from a mean of 50.4+/-11.1 mg/dL to 44.4+/-8.5 mg/dL after 3 months of megestrol acetate therapy (p<0.05). Serum total cholesterol level significantly lowered from a mean of 222.8+/-50.0 mg/dL to 192.7+/-36.5 mg/dL (p<0.05) and apolipoprotein A-I level from a median of 134 mg/dL to 116 mg/dL (p<0.05) after the therapy. Serum LDL-cholesterol, triglyceride, apolipoprotein B, fasting and 2-h postprandial glucose levels did not significantly change after the therapy (p>0.05). The median weight of patients was found to be 70 (53-110) kg before the therapy and 74 (56-111) kg after the therapy (p=0.001). CONCLUSIONS: The use of megestrol acetate, 160-320 mg/d, in the treatment of endometrial pathology is an effective method without marked harmful effects on serum lipid profiles or glucose levels but is associated with weight gain.     

Postoperative radiotherapy in stage I endometrial adenocarcinoma

OBJECTIVE: To evaluate postoperative whole pelvic radiation for high-risk patients with Stage I endometrial adenocarcinoma. METHODS: One hunderd and twenty-two patients with irregular premenopausal or postmenopausal haemorrhage were included into the study. Fractional curettage was performed in all cases. When the pathohistological report confirmed endometrial adenocarcinoma, abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. Low-risk patients include women with Stage IA tumours and Stage IB grade 1 or 2 histology. High-risk group include patients with Stage IB grade 3 tumours and Stage IC carcinomas. High-risk patients received whole pelvic radiotherapy between two and four weeks after surgery. RESULTS: Eighty-two patients (67.21%) were low-risk and forty patients (32.79%) were high-risk. In the low-risk group of patients, CA-125 was negative in ten cases and positive in 72 patients with a mean value of 30.12 +/- 12.42 U/ml serum. In the high-risk group of the patients, CA-125 was negative in two cases and positive in 38 patients with a mean value of 60, 48 +/- 20, 14 U/ml serum. Locoregional recurrences were diagnosed in four patients (4.87%) in the surgery group and in two patients (5.00%) assigned to radiotherapy. The incidence of distant metastases was 2.43% in the surgery group and 2.50% in the radiotherapy group. Overall survival at five years was 90.25% in the low-risk group and 87.50% in the high-risk group of patients. CONCLUSION: Five-year overall survival, locoregional and distant metastasis were similar in the low-risk and high-risk groups of patients. That emphasizes the value of whole pelvic radiation in patients with unfavourable prognostic factors in Stage I endometrial cancer.     

Plasma medroxyprogesterone acetate levels following intramuscular or oral administration in patients with endometrial adenocarcinoma.

The concentration of medroxyprogesterone acetate (MPA) in plasma samples taken 24 h after intramuscular or oral administration of 100 mg daily doses of the drug to patients with endometrial adenocarcinoma was measured by radioimmunoassay. In general, a plasma level of about 4 ng/ml was found 24 h after the dose, independent of the route of drug administration. However, in three of the patients to whom intramuscular MPA was given, considerably higher values were found. A maximal plasma level was achieved three hours after ingestion of 100 mg MPA. This was followed by a rapid decline to 20-25% of the peak value after about 12 h. A rather small day-to-day intraindividual variation was found in daily blood samples taken just before administration of the next dose. However, considerable differences were found between individuals and it is concluded that this variation in plasma levels may be reflected in the clinical efficacy of the treatment. Thus further studies in which plasma values and clinical effectiveness are correlated seem to be indicated.     

Pregnancy outcome in patients treated with cervical conization for cervical intraepithelial neoplasia

Objective

To examine the causal contribution of conization to premature delivery.

Methods

This was a retrospective, case-control, multicenter study of women who underwent conization in 5 hospitals in the Basque Country (Spain) from 1998 to 2007. Three study groups were established: group A, post-conization infant deliveries; control group B, pre-conization infant deliveries; and control group C, infant deliveries without conization.

Results

Comparing group A with group C, there was a higher rate of preterm delivery before 35 weeks (5.3% versus 1.6%), a lower mean birth weight (3156.2 g versus 3328.5 g), and a greater prevalence of infants under 2500 g (10.6% versus 3.7%). There were no significant differences between group A and group B: preterm delivery before 35 weeks (5.3% versus 4.8%), mean birth weight (3156.2 g versus 3119.4 g), and prevalence of infants under 2500 g (10.6% versus 10.6%).

Conclusion

Pregnancy in women post-conization was associated with a risk of preterm delivery. However, there were no significant differences between women who underwent conization before and those who underwent conization after delivery. Cervical conization does not necessarily increase the risk of preterm delivery in subsequent pregnancy. Conization should be considered an indicator of such risk because it is associated with pregnancy complications arising from socio-epidemiologic factors present in women requiring conization that are also present in women who have premature delivery.     

Pelvic radiation in stage I endometrial adenocarcinoma with high-risk attributes

From 1977 to 1987, 45 patients with FIGO stage I endometrial adenocarcinoma with high-risk attributes and disease confined to the pelvis were prospectively treated with postoperative pelvic radiation. By study design, all patients underwent staging laparotomy with pelvic and paraaortic lymphadenectomy. All patients had either grade 1 or 2 adenocarcinoma and greater than 50% myometrial invasion or grade 3 adenocarcinoma with less than or greater than 50% myometrial invasion. The estimated 5-year survival for all 45 patients was 77% and the 5-year disease-free interval was 82%. Regional control was achieved in 89% of all patients, with 4% recurring at distant sites. When patients were stratified according to surgical-pathologic findings, 33 patients with disease confined to the uterus or uterus and pelvic nodes (surgical stage I) had estimated 5-year survival and disease-free interval of 88%. Of these 33 patients, 10 with grade 1 or 2 adenocarcinoma and deep myometrial invasion had 5-year disease-free intervals of 100%, while 23 patients with grade 3 adenocarcinoma with less than or greater than 50% myometrial invasion had disease-free intervals of 79 and 91%, respectively. From these results, it was concluded that patients with high-risk attributes demonstrated to have disease confined to the uterus or uterus and pelvic nodes can achieve excellent survival following surgical staging and postoperative pelvic radiation.