Successful conservative treatment of endometrial carcinoma permitting subsequent pregnancy: report of two cases

Two women with endometrial carcinoma who wished to preserve their childbearing ability received conservative treatment by medroxyprogesterone acetate (MPA, 600 mg/day for 22 weeks and 29 weeks, respectively). Following regression of endometrial lesions, their infertility was treated by inducing ovulation. Intact pregnancy was diagnosed 13 months and 11 months after completion of the MPA treatment, respectively. One patient had a twin pregnancy and delivered two infants at 35 weeks of gestational age. The other patient delivered a full-term baby. They had no evidence of recurrence 60 months and 31 months after the conservative treatment, respectively. We believe this conservative treatment with progestin may be safely performed for young patients with endometrial cancer who wish to preserve their fertility.     

Fertility preserving options in patients with gynecologic malignancies

A proportion of reproductive age women are affected by gynecologic malignancies. This patient population is faced with difficult decisions, related to their cancer care and treatment, as well as future childbearing potential. Therefore, it is important for gynecologists to be familiar with fertility sparing management options in patients with cervical, ovarian, and endometrial cancer. In addition to understanding the surgical approaches available, providers should be able to counsel patients regarding their eligibility for and the indications and limitations of fertility sparing therapy for gynecologic cancer, allowing for appropriate referrals. A comprehensive PUBMED literature search was conducted using the key words "fertility preservation," "cervical cancer," "endometrial cancer," "ovarian cancer," "borderline tumor of the ovary," "germ cell tumor," "obstetrical outcomes," "chemotherapy," and "radiation." The following review summarizes fertility sparing options for patients with cervical, ovarian and endometrial cancer, with an emphasis on appropriate patient selection, oncologic, and obstetric outcomes.     

Fertility Preservation in Young Women with Breast Cancer

Approximately 10,000 cases of breast cancer are diagnosed in women younger than 40 years of age each year in the United States. This creates a population of young women with breast cancer who may have not started or completed their family. Given that technology and treatment have improved outcomes for these women, quality of life issues, such as fertility preservation, must be considered. This review examines breast cancer patient and physician attitudes toward fertility preservation, ovarian toxicity of chemotherapeutic agents, fertility preservation options for breast cancer patients, and the safety of subsequent pregnancies for these women.     

Infertility-associated endometrial cancer risk may be limited to specific subgroups of infertile women

Data from previous studies suggest that infertility is a risk factor for endometrial cancer. We used data from the Cancer and Steroid Hormone Study to further characterize this relationship. The subject group comprised 399 women ages 20-54 with newly diagnosed epithelial endometrial cancer ascertained through six cancer registries. The control group comprised 3040 women in the same age range selected by random-digit telephone dialing from the same geographic areas where cancer patients resided. Compared with women who reported no fertility problem, women with physician-diagnosed infertility who had reported at least 2 years of infertility had an odds ratio for endometrial cancer, adjusted for age, of 1.7 (95% confidence interval 1.1-2.6). Women who reported infertility resulting from ovarian factors had an adjusted odds ratio of 4.2 (95% confidence interval 1.7-10.4). These results suggest that factors such as anovulation may explain much of the increased risk of endometrial cancer found among subgroups of infertile women.     

Endometrial cancer

Endometrial carcinoma is the most common gynaecological malignancy in the Western world. The standard management of endometrial carcinoma is total hysterectomy and bilateral salpingo-oophorectomy with or without pelvic and para-aortic lymph-node dissection. Increasingly, endometrial cancer is being diagnosed in younger women in whom preserving fertility may be an important consideration when deciding optimal management. Conservative management of endometrial carcinoma may be a therapeutic option in carefully selected women with well-differentiated endometrial cancer in the absence of any myometrial invasion or adnexal disease seen on imaging. The biggest concern with conservative management of endometrial carcinoma is disease progression while on treatment or after initial response to medical treatment. Women opting for conservative management should be aware that hormonal therapy is not the standard form of management. Potential adverse outcomes should be taken into consideration.     

A successful live birth with in vitro fertilization and thawed embryo transfer after conservative treatment of recurrent endometrial cancer

Estrogen-dependent early stage endometrial cancer is relatively common in young women of reproductive age. The standard treatment is hysterectomy and bilateral salpingo-oophorectomy (BSO), even in early stage well-differentiated endometrial cancer patients. This surgical option results in permanent loss of fertility. There have been some reports of live births using in vitro fertilization after conservative management of endometrial cancer with high-dose progestin for the purpose of fertility preservation. However, most were not recurrent cases and pregnancy was achieved through conventional in vitro fertilization, which usually raises serum estradiol levels and may lead to the recurrence of endometrial cancer. To date, it is hard to find a case that can be referred for any possible different approach needed for the patients who experience recurrence. Here we report a successful live birth with in vitro fertilization using letrozole to maintain physiological levels of estradiol, and subsequent thawed embryo transfer after elective cryopreservation of embryos in a patient with recurrent endometrial cancer. There has been no evidence of disease recurrence at one year after delivery.     

Safe fertility-preserving management in gynecological malignancies

Objective To provide a review in the available literature about the safe fertility-preserving management in gynecological malignancies, focusing on the selection criteria of the patients, treatment options and follow-up. Design Literature survey. Results The incidence of cancer in women who still want to get pregnant is increasing significantly. An early detection in gynecological malignancies allows less aggressive approaches to cure such disorders. A more conservative management, which preserves fertility, is considered safe and an option for those who have not completed their child-bearing. Conclusions Selected patients with cervical, endometrial and ovarian cancer may be candidates to a safe fertility-preserving management. A careful stage and follow-up of the patients is essential to achieve success with this practice.     

Fertility preservation options for female patients with malignancies

PURPOSE OF REVIEW: Preservation of fertility in female patients diagnosed with cancer has recently been an area of intensive investigation. This review summarizes available options and discusses recently published data concerning experimental methods. Specific strategies for fertility preservation in women with gynecologic malignancies are also presented. RECENT FINDINGS: Success with ovarian stimulation protocols using tamoxifen or aromatase inhibitors has recently been reported for women with breast cancer who attempt embryo cryopreservation prior to chemotherapy. The first embryo transfer using oocytes retrieved from cryopreserved ovarian tissue implanted at a heterotopic location, the first pregnancy following orthotopic transplantation of cryopreserved ovarian tissue, and increasing success with oocyte cryopreservation were also reported. SUMMARY: Fertility preservation in female patients with cancer has become an important health issue due to increasing survival rates and delayed childbearing especially in Western countries. Radical vaginal trachelectomy for cervical cancer, conservative surgery for ovarian tumors, and progestin treatment in endometrial cancers may be considered at early stages in order to preserve fertility. Embryo cryopreservation is an established technique that is available for fertility preservation, providing a delay in the initiation of chemotherapy or radiotherapy is acceptable, and a partner or donor sperm is available. Additional techniques that could be offered after counseling the patient about their experimental nature include oocyte cryopreservation, ovarian cryopreservation, and gonadotropin-releasing hormone agonist co-treatment with chemotherapy. Improvement of these techniques as well as better characterization of their success rates and risks await further investigation.     

Challenges and controversies in the conservative management of uterine and ovarian cancer

Uterine cancer is the fifth most common cancer in women worldwide with an estimated 320,000 annual diagnoses. Its most common form, endometrioid adenocarcinoma of the endometrium (endometrial adenocarcinoma [EAC]), is thought to develop through excessive proliferation of endometrial glands, and then increasing steadily in incidence. The current standard treatment for EAC is hysterectomy, which is often curative. However, it may be unacceptably expensive for women with severe medical comorbidities, those who are at risk of intra- and postoperative adverse events and those who desire fertility.Ovarian cancer is the most malignant of all gynaecological cancers, but patients with disease limited to one ovary and patients with non-epithelial tumours may expect a good prognosis. A selected group of young patients who desire fertility may be well treated with conservative surgery.This chapter reviews patient selection, diagnosis, pre-treatment evaluation, treatment options, surveillance and risk of relapse.     

Fertility Sparing Surgery in Gynecologic Cancer

Fertility preservation is one of the major concerns of young patients diagnosed with gynecological cancer. With newer treatment regimens and better surgical techniques, survival rates after cancer treatment have improved, hence preservation of fertility has recently become an important issue in the treatment of gynecological cancers. Fertility sparing surgery may be an option for early-stage cervical cancer with the development of loop excision techniques and radical trachelectomy which allows a radical approach to cervix cancer at the same time preserving the uterus and thus fertility. Fertility preservation is possible in Stage 1 epithelial ovarian cancers, germ cell ovarian tumors, and borderline cancers. Hormonal therapy with progestin agents is effective in early endometrial cancer. In patients desiring future pregnancy, fertility sparing options must be explored before starting treatment for gynecologic cancers.     

Endometrial cancer and fertility

PURPOSE OF REVIEW: Endometrial cancer can affect reproductive-age women who may desire fertility preservation. This article discusses the current, available data about conservative management of endometrial cancer in young women. RECENT FINDINGS: Reproductive-age women with well differentiated endometrial carcinoma have an overall favorable prognosis provided that the tumor is identified at an early, noninvasive stage; however, advanced disease can be present. This article discusses current modalities to evaluate and clinically stage endometrial cancer including hysteroscopy, dilation and curettage, pelvic ultrasound, abdominopelvic computed tomography scan, pelvic magnetic resonance imaging, tumor marker CA125 level, and surgical exploration with laparoscopy or laparotomy. Thorough evaluation is critical as 10 to 29% of young women with endometrial cancer have a synchronous ovarian malignancy. Detailed counseling about the risks and benefits of conservative management, and expectations for fertility after treatment, surveillance, and definitive surgical management is essential. Multiple effective protocols exist for conservative treatment of endometrial cancer, and the initial response rates are as high as 57 to 75%. Successful pregnancies have occurred after conservative management, spontaneously, and with assisted reproductive technologies. SUMMARY: There are no standard recommendations for selection of appropriate women, treatment protocols, or long-term surveillance for conservative management of clinical stage I endometrial adenocarcinoma, and larger prospective clinical studies are warranted.     

Fertility-sparing management of endometrial adenocarcinoma

Approximately 15% of patients with endometrial cancer are premenopausal. Previous studies largely support the conservative treatment of endometrial cancer in women desiring future fertility. From these studies, 75% to 80% of patients demonstrate a complete response to progestin therapy and the average recurrence rate is 30% to 35%. Conservative therapy should be reserved for women with International Federation of Gynecology and Obstetrics grade I tumors. Before conservative management, patients should be informed of the elevated risk (11%-29%) of concurrent ovarian cancer in cases of premenopausal endometrial cancer, and screening and ongoing surveillance during the treatment period is mandatory. A suggestion of myometrial invasion or metastatic disease is a contraindication to conservative management. Individuals meeting criteria for Lynch syndrome testing should be referred to genetic counseling. Fertility treatment should be individualized, and close surveillance is required during treatment. Staging hysterectomy is recommended after the completion of the childbearing period. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After participating in this activity, physicians should be better able to select appropriate candidates with endometrial cancer for fertility-sparing treatment. Educate patients with endometrial cancer regarding the risks and benefits of standard of care therapy and conservative therapy and screen appropriate patients for Lynch syndrome.     

子宫内膜癌保留生育功能的治疗

未生育的年轻子宫内膜癌患者常常寻找保留生育功能的治疗方法。本文的主要目的是复习有关子宫内膜癌患者保留生育功能治疗的相关文献,探讨适合进行保留生育功能治疗的患者特征、治疗前的评估、治疗方案、疗效以及妊娠率。     

Endometrial hyperplasia: a review

Endometrial hyperplasia is a precursor to the most common gynecologic cancer diagnosed in women: endometrial cancer of endometrioid histology. It is most often diagnosed in postmenopausal women, but women at any age with unopposed estrogen from any source are at an increased risk for developing endometrial hyperplasia. Hyperplasia with cytologic atypia represents the greatest risk for progression to endometrial carcinoma and the presence of concomitant carcinoma in women with endometrial hyperplasia. Abnormal uterine bleeding is the most common presenting symptom of endometrial hyperplasia. Specific Pap smear findings and endometrial thickness per ultrasound could also suggest the diagnosis. Unopposed estrogen in women taking hormone replacement therapy increases the risk of endometrial hyperplasia. Tamoxifen has demonstrated its efficacy in treating women at risk for breast cancer, but it increases the risk of endometrial hyperplasia. The choice of treatment for endometrial hyperplasia is dependent on patient age, the presence of cytologic atypia, the desire for future childbearing, and surgical risk. Endometrial hyperplasia without atypia responds well to progestins. However, women with atypical hyperplasia should be treated with hysterectomy unless other factors preclude surgery. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to describe the definition and classification of endometrial hyperplasia, to outline the clinical features of a patient with endometrial hyperplasia, to point out the natural history of endometrial hyperplasia, and to summarize the diagnostic options for patients with endometrial hyperplasia.     

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。     

Oncofertility for women with gynecologic malignancies

The emerging field of oncofertility addresses fertility and the reproductive health needs for cancer patients, a key topic in cancer survivorship. Given that the standard treatment for gynecologic malignancies involves removal of reproductive organs, pelvic radiation, or chemotherapy, the effect of such treatment on fertility and options for fertility preservation are even more relevant than for other malignancies.In young women with new diagnoses of cervical, endometrial, or ovarian cancers, viable strategies for fertility preservation without compromising oncological outcome exist and should be considered. We present here a comprehensive review of the literature as it pertains to gynecologic malignancies on 1) the effects of radiation and chemotherapy on fertility, 2) fertility-sparing surgeries and the role of assisted reproductive technology, and 3) fertility preservation in adolescent girls and women with BRCA germline mutations.     

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.     

Hormone therapy for younger patients with endometrial cancer

The relationship between hormones and endometrial cancer is well known because disease states, such as chronic anovulation and endogenous estrogen production from hormone-secreting tumors (for example, granulosa cell tumor of the ovary), are related to excess estrogen, and unopposed estrogen use might lead to endometrial overgrowth, hyperplasia, and subsequent development of endometrial carcinoma. Therefore, the possibility of using antihormone therapy in endometrial carcinoma and/or its precancer lesions, such as simple hyperplasia with and without atypia and complex hyperplasia with and without atypia, is always supposed, as in the management of breast cancer. In addition, if women in whom endometrial cancer is diagnosed are very young, some critical issues should be considered, including the possibility of ovary preservation-partial preservation of fertility and the possibility of both ovary and uterus preservation-complete preservation of fertility. Other factors are also important to consider and include oncologic risk, appropriateness of candidates for treatment, type of hormone use, response rate of hormonal therapy, appropriate surveillance, and additional counseling for issues such as anxiety about relapse and metastasis, distress about side effects, advice of the family, advice of the medical staff, and economic burden.This review will be focused on updated information and recent knowledge of the use of hormones in the management of younger women with endometrial cancer who want fertility preservation.     

Fertility-preserving treatment in young women with endometrial cancer

Nonsurgical fertility-preserving treatment of well-differentiated endometrial cancer with systemic progestins has been described for young women who desire to preserve their fertility. The overall response to progestin treatment in 9 retrospective studies is 79% with 79 subsequent live births. Recurrence can be expected in approximately 36-40% of conservatively treated patients who initially responded. Synchronous ovarian cancer has been reported in approximately 9%. However, amongst 162 receiving systemic, continuous treatment with progestins no death caused by cancer has been reported. We review guidelines for diagnosis, treatment and follow-up in young women undergoing conservative treatment for endometrial cancer.     

Fertility-preserving surgical procedures for patients with gynecologic malignancies

Gynecologic malignancies often affect young women who are at the peak of their reproductive potential. The treatment for gynecologic malignancies often consists of removal of the ovaries or uterus, affecting the future fertility of these patients. Advances in surgical management have allowed patients to undergo more conservative treatment with preservation of their fertility. This review summarizes fertility-sparing surgical procedures for patients with gynecologic malignancies evaluating the role of radical trachelectomy and ovarian transposition in cervical cancer, hormonal therapy and hysteroscopic resection in endometrial cancer, and conservative surgery in ovarian cancer.