Pregnancy outcomes of women who received conservative therapy for endometrial carcinoma or atypical endometrial hyperplasia

Case

Approximately 3%‐25% of cases of endometrial carcinoma (EC) or atypical endometrial hyperplasia (AH) occur in women aged <40 years and conservative treatment with high‐dose medroxyprogesterone acetate (MPA) is administered to women who wish to preserve their fertility. Here is reported the pregnancy outcomes of patients with EC or AH who received MPA therapy at Tokushima University Hospital, Tokushima, Japan. The frequency of pregnancy and live births among the patients with EC or AH who received conservative treatment, followed by fertility treatment, were analyzed retrospectively.

Outcome

Twelve patients underwent fertility examinations and received fertility treatment immediately after the completion of conservative treatment for EC or AH. One patient had the complication of severe diabetes and total embryo cryopreservation was performed before her diabetes was treated. Among the other 11 patients, 8 (72.7%) became pregnant at least once and 6 (54.5%) experienced at least 1 live birth. Three patients (25.0%) suffered disease recurrence during or after the infertility treatment and all of the recurrences occurred in the EC cohort.

Conclusion

When patients with EC or AH wish to preserve their fertility, it is recommended that prompt and effective fertility treatment, including assisted reproductive technology, should be initiated just after conservative treatment because EC and AH exhibit relatively high recurrence rates among conservatively treated patients.     

Endometrial carcinoma remaining after term pregnancy following conservative treatment with medroxyprogesterone acetate

BACKGROUND: Successful pregnancies after conservative progestin treatment to young women with endometrial carcinoma have recently been reported. However, it is not known for certain whether the lesion is completely eradicated in such patients. We present a case of residual endometrial carcinoma after term pregnancy which had been treated conservatively before the pregnancy began. CASE: A 28-year-old woman with endometrial carcinoma received conservative treatment with high-dose medroxyprogesterone acetate (MPA) and then conceived. After delivery at term, atypical cells were found in the endometrial curettage specimen. A hysterectomy was performed 6 months after delivery and revealed the presence of a small focus of intramucosal, grade 1, endometrioid-type adenocarcinoma. Immunohistochemically, the tumor cells were positive for estrogen and progesterone receptors. CONCLUSION: We concluded that while MPA treatment had been effective, it had not completely eradicated the carcinomatous lesion, which remained during and after the term pregnancy.     

宫腔镜联合孕激素治疗年轻患者早期子宫内膜癌的疗效及预后分析

目的:探讨宫腔镜联合孕激素治疗年轻早期子宫内膜癌患者的疗效及预后。方法:回顾性分析四川大学华西第二医院2008年1月至2014年12月自愿接受宫腔镜联合孕激素治疗的年轻早期子宫内膜癌16例患者的临床资料,且随访资料完整。所有患者行宫腔镜下刮宫或宫腔镜下病灶切除+刮宫,其中7例联合口服醋酸甲羟孕酮(250 mg/d,MPA组),9例联合醋酸甲地孕酮(160 mg/d,MA组)治疗。比较两组患者缓解、复发及生育等情况。结果:随访中位时间为54个月(17~90个月),其中12例(75.0%)完全缓解,3例(18.8%)部分缓解,1例(6.2%)无反应,MPA组和MA组的完全缓解率分别为71.4%(5/7)和77.8%(7/9),差异无统计学意义(P0.05)。16例患者中有3例在完全缓解后复发(MPA组1例,MA组2例),复发平均时间为42个月。16例患者中有8例(50.0%)完成了妊娠(其中1例2次妊娠),有6次(66.6%)妊娠顺利生产,3次(33.3%)流产。结论:宫腔镜联合孕激素治疗对于年轻早期子宫内膜癌患者保守治疗是有效的,其中MPA和MA的治疗效果无明显差异,但均存在着一定的复发风险,所以应对其进行严格的筛选和严密的随访。     

Ectopic pregnancy after successful treatment with percutaneous transcatheter uterine arterial embolization for congenital uterine arteriovenous malformation: a case report

INTRODUCTION: Uterine arteriovenous malformation (AVM) is a rare disease. Percutaneous transcatheter uterine arterial embolization (UAE) has been performed in patients who wish to preserve their ability to conceive. UAE is considered to be a safe and effective procedure, but its long-term effect on fertility has not been fully elucidated. We present a case of ectopic tubal pregnancy after conservative treatment with UAE for uterine AVM. CASE: A 30-year-old Japanese woman was admitted for the treatment of unruptured right tubal pregnancy at 6 weeks of gestation. She had conceived spontaneously and delivered a healthy baby at term, 3 years previously. Subsequently, she was successfully treated with UAE for a large congenital uterine AVM. Transvaginal color Doppler ultrasonography revealed no evidence of residual AVM vessels. After the diagnosis of ectopic pregnancy, the patient underwent right tubectomy. At laparotomy, there were no adhesions or structural anomalies in the pelvic cavity that might affect tubal function. The patient's postoperative course was uneventful, and she is now healthy without conception 24 months after surgery. CONCLUSION: Prior uterine arterial embolization may have affected the tubal function in the present case, allowing tubal pregnancy to occur.     

高分化子宫内膜样癌及子宫内膜重度不典型增生患者孕激素治疗的临床分析

目的探讨35岁以下高分化子宫内膜样癌及子宫内膜重度不典型增生患者采用孕激素治疗以保留患者子宫的疗效,并随访其治疗后的生育情况.方法采用回顾性分析的方法对1991年至2005年北京协和医院收治的35岁以下、接受孕激素治疗（以醋酸甲羟孕酮为主）的25例高分化子宫内膜样癌及子宫内膜重度不典型增生患者的临床病理资料进行研究.其中,子宫内膜样癌8例（内膜癌组）,子宫内膜重度不典型增生17例（不典型增生组）.孕激素治疗前对患者进行全面的分期评估,治疗后每1～6个月诊刮以评价疗效,对有生育要求者随访其生育情况.结果内膜癌组患者孕激素治疗前经全面的分期评估,证实为早期、高分化子宫内膜样癌.除1例子宫内膜样癌患者尚未评估疗效外,内膜癌组其他7例及不典型增生组17例患者治疗后有效者分别为6例（6/7）、17例（100%）;缓解者分别为5例（5/7）、14例（82%）;缓解后复发者分别为1例（1/5）、3例（21%）,复发时间为缓解后6～30个月;随访缓解后要求生育的14例患者中,内膜癌组4例患者尚未生育,不典型增生组10例患者中4例妊娠共7次.1例自然受孕后失访;3例经促排卵治疗后受孕并足月分娩,其中1例产后人工流产3次.结论对于要求保留子宫的高分化子宫内膜样癌及子宫内膜重度不典型增生的年轻患者,孕激素治疗是一种治疗选择.孕激素治疗前应对子宫内膜样癌患者进行详细全面的分期评估,辅助生殖措施的介入有望提高治疗后的妊娠率.     

Progression of conservatively treated endometrial carcinoma after full term pregnancy: a case report

INTRODUCTION: We describe a case of conservatively treated endometrial endometrioid (EE) adenocarcinoma which showed an aggressive clinical outcome after pregnancy. CASE: A 30-year-old woman with a well differentiated EE adenocarcinoma decided to attempt a conservative approach and underwent progestin treatment with subsequent negative ultrasound and hysteroscopic controls. After 3 months, she conceived and at 36 weeks of gestation, a cesarean section was performed with multiple negative biopsies. Eight 8 months after delivery, an exploratory laparotomy documented disseminated poorly differentiated EE adenocarcinoma. Staging work up revealed diffuse metastatic disease. Despite chemotherapy, the patient experienced progression of disease with fatal acute respiratory syndrome due to massive neoplastic pulmonary lymphangitis. CONCLUSION: Conservative medical management of endometrial cancer in young women willing to preserve their reproductive potential, carries on potential risks. Careful selection of cases, informed consent, and strict follow up procedures are mandatory.     

Pregnancy following intracytoplasmic sperm injection and preimplantation genetic diagnosis after the conservative management of endometrial cancer

A rare case of a patient with conservatively treated endometrial carcinoma who conceived and delivered a healthy baby after the transfer of embryos with intracytoplasmic sperm injection (ICSI) and preimplantation genetic diagnosis (PGD) is presented. A 41-year-old woman had an office hysteroscopy in the infertility work-up and stage I endometrial adenocarcinoma was diagnosed. After conservative treatment, the patient underwent ICSI and PGD. She achieved pregnancy with two normal embryos. Two gestational sacs were observed but one of them was blighted. The patient subsequently delivered a healthy female infant. Repeated office hysteroscopy and endometrial sampling was performed after delivery. The appearance of the endometrium was normal on hysteroscopy, and the histology report was normal. The principal concern with medical therapy is that the lesion cannot be fully evaluated until the hysterectomy is performed, the nodes palpated, and the uterus is sectioned. The patient was referred to a gynaecological oncologist for definitive surgery.     

Case of atypical polypoid adenomyoma that possibly underwent a serial progression from endometrial hyperplasia to carcinoma

Atypical polypoid adenomyoma is a rare uterine tumor composed of atypical endometrial glands, which often exhibit squamous metaplasia, and a cellular smooth muscle stroma. Although atypical polypoid adenomyoma is categorized as a benign lesion, it is reportedly associated with endometrial cancer, and it shows persistence and recurrence even after conservative medical treatment. We present a rare case of atypical polypoid adenomyoma that possibly underwent a serial pathological change from endometrial hyperplasia to carcinoma in a 40-year-old woman with no history of pregnancy. She was diagnosed with atypical polypoid adenomyoma during polypectomy surgery. After resecting the atypical polypoid adenomyoma, endometrial hyperplasia complex was detected. This condition eventually progressed from atypical hyperplasia complex to endometrial adenocarcinoma, and total abdominal hysterectomy was performed. A patient with atypical polypoid adenomyoma who wishes to preserve her fertility should be carefully monitored for endometrial carcinoma. If endometrial hyperplasia is detected in such a patient, a meticulous follow-up examination by performing endometrial biopsy is mandatory.     

Tratamiento conservador del adenocarcinoma de endometrio. Obtención de dos gestaciones con recién nacidos sanos

We present the case of a 30-year-old childless woman who was diagnosed with a well-differentiated endometrial adenocarcinoma. The patient chose conservative treatment consisting of megestrol and hysteroscopic resection. After this treatment, a normal pregnancy ensued, followed by contraception with an intrauterine device (IUD) delivering levonorgestrel for 18 months. After removal of the IUD, a second normal pregnancy occurred. After the second pregnancy, the patient had no desire for more children and a total hysterectomy with bilateral salpingo-oophorectomy was performed. We discuss the ethical, diagnostic and therapeutic dilemmas posed by this case, including the possibility of progression and patient death.     

Successful pregnancy in an infertile woman with endometrial hyperplasia and embryo transfer. A case report

BACKGROUND: Successful pregnancy in a woman with complex endometrial hyperplasia with atypia was treated conservatively with gestagens. CASE: The patient was initially diagnosed with complex hyperplasia of the endometrium with atypia by endometrial curettage and treated with several cycles of different gestagens. After repeated endometrial curettage, in vitro fertilization and embryo transfer were introduced for immediate treatment of the patient's infertility in order to avoid the risk of recurrent hyperplasia of the endometrium from estrogens. A single pregnancy was achieved after transfer of embryos obtained from intracytoplasmic sperm injection. This was performed due to poor semen characteristics. The patient delivered a normal, healthy male infant at term. CONCLUSION: Conservative treatment of complex endometrial hyperplasia with atypia in young women wishing to preserve fertility should be considered in carefully selected cases.     

Fertility-preserving treatment of stage IA,well-differentiated endometrial carcinoma in young women with hysteroscopic resection and high-dose progesterone therapy

Objective

The standard treatment for endometrial cancer is surgery with hysterectomy. However, this procedure will cause infertility in young women who desire to preserve pregnant ability. Conservative management with hormone therapy has been shown to be satisfactory in both tumor control and fertility preservation. Recently, hysteroscopic tumor resection followed by progestin therapy has been reported to be an alternative strategy. In this study we present our experience with this approach.

The fertility-sparing treatment in patients with endometrial atypical hyperplasia and early endometrial cancer: A debated therapeutic option

Fertility-sparing treatment may represent a realist option for accurately selected young patients with endometrial atypical hyperplasia or well differentiated, early endometrial cancer. Oral progestins, and especially medroxyprogesterone acetate (MPA) and megestrol acetate with different doses and schedules, represent the most commonly used hormone agents in this clinical setting. Approximately three fourths of the women achieve a histologically documented complete response, with an mean response time of 12 weeks, but about one third of these subsequently developed a recurrence after a mean time of 20 months. The expression of receptor for progesterone receptor (PR), PTEN gene, DNA mismatch repair gene MLH1 and phospho-AKT on tissue specimens may be useful for selecting patients fit for a conservative management. Several successful pregnancies have occurred after a fertility-sparing treatment of endometrial atypical hyperplasia or endometrial cancer, more frequently with assisted reproductive technologies. The implementation of in vitro fertilisation techniques not only increases the chance of conception, but it may also decrease the interval to conception. The opportunity of a demolitive surgery after delivery or after childbearing being no longer required is a still debated issue. Large multicenter trials are strongly warranted to better define the selection criteria for a conservative treatment, endocrine regimen of choice, the optimal dosing, the duration of treatment and follow-up protocols. In any case, the patient should be accurately informed about the relatively high recurrence rates after complete response to hormone treatment and expectations for pregnancy.     

A patient with stage 1a endometrial carcinoma in whom a solitary recurrent lesion was detected in the external iliac lymph node after MPA therapy

BACKGROUND: In the treatment of endometrial carcinoma, young patients desire the preservation of the uterus, and therefore hormonal therapy has been administered. CASE REPORT: The patient was a 39-year-old nullipara diagnosed with stage 1a endometrial carcinoma. The patient desired the preservation of the uterus, and oral administration of MPA was prescribed for 18 weeks, which after the cancer tissue disappeared. However, about 1 year and 6 months later, the patient was diagnosed as having recurrent endometrial carcinoma in the left external iliac lymph node. CONCLUSION: In the literature, there is no patient with relapse at another site in the absence of endometrial relapse after MPA therapy for stage 1a endometrial carcinoma, as performed in the present patient.     

Successful in vitro fertilization pregnancy after conservative management of endometrial cancer

OBJECTIVE: To report a successful IVF pregnancy in an infertile couple after conservative treatment of endometrial cancer. DESIGN: Case report and literature review. SETTING: University teaching hospital. PATIENT(S): A 29-year-old infertile white woman. MAIN OUTCOME MEASURE(S): Successful pregnancy after conservative management of endometrial cancer. INTERVENTION(S): Grade 1 endometrial adenocarcinoma diagnosed at hysteroscopy, followed by dilatation and curettage (D&C). On follow-up D&C, pathologic examination was normal after high-dose progesterone therapy. The patient subsequently underwent an IVF cycle with transfer of three blastocysts. RESULT(S): The patient delivered triplets by cesarean section. Laparoscopic-assisted vaginal hysterectomy and bilateral salpingo-oophorectomy was then done. No residual endometrial cancer was evident in the hysterectomy specimen, but a 1.1-cm cystic mixed endometrioid and clear cell-type adenocarcinoma was discovered in the left ovary. The patient is doing well after 3 cycles of chemotherapy; her CA-125 level is normal. The triplets are also doing well. CONCLUSION(S): In carefully chosen situations, deferring surgery in infertile patients with endometrial cancer may be a viable option permitting subsequent successful pregnancy.     

子宫内膜不典型增生和早期子宫内膜癌保守治疗方案分析

随着癌症发病的年轻化,患有子宫内膜癌的育龄期女性越来越多。为了保留生育能力,大部分患者倾向于保守治疗。故而众多研究者提出了子宫内膜不典型增生和早期子宫内膜癌的保守治疗方案,并在临床上进行了小样本研究。传统治疗以口服大剂量孕激素为主,然而多数口服孕激素治疗的患者复发率高、并发症多。左炔诺孕酮宫内缓释节育系统通过局部作用于子宫内膜,可减少大量孕激素对机体造成的不良反应。宫腔镜能够精准切除病灶,保护正常子宫内膜,相对降低了发生不孕、流产风险。二甲双胍的抗肿瘤作用能增加孕激素的有效率。通过综述子宫内膜不典型增生和早期子宫内膜癌各种保守治疗后的缓解率、复发率和妊娠结局,为临床上在治疗前对每位患者的自身因素及疾病特点进行评估,以采取对患者最有益的治疗方案及管理模式提供依据。     

Treatment for complex atypical hyperplasia of the endometrium.

OBJECTIVE: To clarify the clinical outcome of women with complex atypical hyperplasia of the endometrium who were treated either by hysterectomy or a non-surgical treatment with medroxyprogesterone acetate (MPA). STUDY DESIGN: Thirty of the 53 patients with complex atypical hyperplasia of the endometrium were treated by undergoing hysterectomy and 20 were treated with MPA alone as the primary therapy. Their clinical features and outcomes were evaluated. RESULTS: The ages of the 53 patients ranged from 28 to 62 years (mean 46.2). Fifteen (75%) of the 20 patients (8 of 12 with low-dose MPA and 6 of 8 with high-dose MPA) responded initially to MPA therapy. Two of the 12 patients who were treated with low-dose MPA progressed to endometrial adenocarcinoma. Three patients treated with high-dose MPA conceived after treatment having three healthy infants. CONCLUSION: Primary treatment with high-dose MPA is a safe and effective therapy for women with complex atypical hyperplasia of the endometrium who wish to preserve their fertility.     

Tratamiento conservador del cáncer de endometrio en una pareja estéril

Successful conservative management for early-stage low-grade endometrial cancer in young women wishing to preserve fertility has been reported in small series. Although few data are available on assisted reproductive technology (ART) outcomes after conservative management of endometrial carcinoma, ART does not seem to worsen prognosis. We report the case of a 29-year-old woman with a history of primary infertility, who was diagnosed with a well-differentiated endometrial adenocarcinoma (stage Ia), which was treated with high doses of oral progesterone. A successful pregnancy was achieved after ART.     

Obstetric outcomes of pregnancy after conservative treatment of endometrial cancer: case series and literature review

ObjectiveTo evaluate the pregnancy courses and obstetric outcomes in patients conceived after conservative treatment of endometrial cancer.Materials and MethodsCase series and systemic review of pregnancy women after fertility-sparing treatment of endometrial cancer. Patients with early stage endometrial cancer were identified through Tumor Registry in Chang Gung Memorial Hospital between 1990 and 2005 and MEDLINE search. Diagnosed cases were managed by fertility-sparing therapies. Pregnancies followed by assisted reproductive technology and spontaneous or ovulation with intrauterine insemination were designated as Group 1 and Group 2, respectively.ResultsFive livebirths in three patients with two sets of twin pregnancy were delivered. Adding 47 women in the MEDLINE search literature, there were 65 deliveries with 77 livebirths. Groups 1 and 2 had 15 and 50 deliveries, respectively. Group 1 had 23 livebirths including four sets of twins and two sets of triplets, whereas 54 livebirths consisted of two sets of twins and one set of triplets were noted in Group 2 (p = 0.003). Seven preterm deliveries were noted in Group 1 and three in Group 2 (p = 0.001). Cesarean rate was 93.3% versus 22.0% (p < 0.001) in Groups 1 and 2, respectively. Pregnancy-induced hypertension and gestational diabetes mellitus were significant between the two groups (p = 0.035). One mother died of disease after delivery. No neonatal morbidity was reported.ConclusionsFor women who had completed conservative treatments in early endometrial cancer, assisted reproductive technology provided a choice of scheduled conception for those with subfertility or chronic anovulation.     

The combined GnRH-agonist and intrauterine levonorgestrel-releasing system treatment of complicated atypical hyperplasia and endometrial cancer: a pilot study

In this article, we present the results of organ-preserving treatment applied in 24 patients of reproductive age with atypical endometrial hyperplasia or early-stage endometrial cancer. All of them would like to preserve their reproductive potential. Thirteen women with atypical endometrial hyperplasia were treated with the combination of six intramuscular injections of 3.75?mg gonadotropin-releasing hormone agonist (GnRHa) ? leuproreline acetate depot every 4 weeks. After the third injection of 3.75?mg of leuproreline acetate, the levonorgestrel intrauterine hormonal system containing 52?mg levonorgestrel (Mirena^®, Bayer, Germany) was inserted for at least 6 months. In 11 women with stage IA well-differentiated endometrial adenocarcinoma, hormonal therapy included nine intramuscular injections of 3.75?mg of GnRHa every 4 weeks. After the third injection of 3.75?mg of GnRHa, we also inserted a GnRH-IUS (Mirena^®) for at least 12 months. This type of therapy was effective for all these patients and may be offered to be used as an alternative to surgery in women with atypical endometrial hyperplasia or early stage 1A well-differentiated endometrial cancer in women of reproductive age. Three women with endometrial cancer became pregnant and two of them delivered at term and one has an ongoing pregnancy.     

Subsequent pregnancy outcome after conservative treatment of a previous cesarean scar pregnancy

BACKGROUND: To assess pregnancy course and outcome after conservative treatment of a cesarean scar pregnancy. METHODS: During an 8-year period, 15 cases of cesarean scar pregnancies were diagnosed at our institution. Seven of the 14 patients for whom we successfully preserved the uterus became pregnant within 3 years after termination of the scar pregnancy. The year of diagnosis, conservative method and gestational age for these five patients were recorded. Delivery method, time interval between the scar pregnancy and subsequent pregnancy, and maternal and neonatal outcome were evaluated. RESULTS: Seven pregnancies (eight live and one dead baby) were noted. The mean interval between the ectopic pregnancy and subsequent pregnancy was 13.3 months (range 0-34 months). One patient, who became pregnant 3 months after the scar pregnancy was found, suffered uterine rupture at 38.3 weeks' gestational age. Two patients with placental accrete, and one of them who continued the existing intrauterine twin pregnancy after transvaginal sono-guided aspiration of the scar pregnancy received a cesarean hysterectomy at 32 weeks of gestation. The remaining four pregnancies were uneventful, followed by early cesarean sections at 36 weeks. CONCLUSION: The results of this first series of seven subsequent pregnancies after conservative treatment of scar pregnancies are promising. An early cesarean section before over-extension of the uterus and spontaneous labor can help to prevent uterine rupture. Placenta accrete is another severe morbidity of these patients in addition to uterine rupture. Thus a cesarean hysterectomy may be the choice of treatment.