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.     

妇科恶性肿瘤保留生育功能生育结局

子宫颈癌、子宫内膜癌和卵巢癌是妇科常见的三大恶性肿瘤，近年来随着发病的年轻化及女性育龄的推迟，保留生育功能的治疗在妇科恶性肿瘤患者中的应用越来越广泛。在妇科恶性肿瘤保留生育功能的临床诊治中，需联合多学科协作诊疗，在不增加肿瘤复发的情况下，保留患者生育功能，制定个体化治疗方案，提供最佳的生育指导，改善生育结局。     

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.     

Fertility preservation: nonsurgical and surgical options

Improved surveillance and treatment regimens have resulted in decreased mortality rates among cancer patients, allowing these women to focus on survival and quality of life, including the ability to preserve their fertility. The treatments that have improved survival among both adults and children diagnosed with cancer are often gonadotoxic, especially those that employ high doses of alkylating agents and radiation therapy directed near or toward the pelvis. The impact on the ovarian reserve is related to the accelerated depletion of the primordial germ cell pool resulting from these therapies. Nonsurgical approaches to fertility preservation, including embryo cryopreservation from in vitro fertilization, oocyte cryopreservation from controlled ovarian hyperstimulation, and in vitro maturation of oocytes, are discussed. Surgical approaches such as conservative gynecologic surgery, ovarian transposition, and ovarian tissue cryopreservation are reviewed. Guidelines from the American Society for Reproductive Medicine and the American Society of Clinical Oncology classify these treatments into established and experimental procedures, and they provide the practitioner with an optimal approach to preserve the fertility of these patients before the initiation of their cancer therapies.     

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.     

Management of endometrial cancer in young women

Endometrial cancer is the most common gynecologic cancer and its incidence is rising among premenopausal women. Hysterectomy and bilateral salpingo-oophorectomy, traditional treatment for endometrial cancer, causes loss of fertility and ovarian function, both of which can significantly negatively impact a young woman's physical and mental well-being. Recently, conservative management with progestational agents has been reported with success from both oncologic and reproductive perspectives. However, there are no randomized trials comparing conservative versus surgical therapy. Patients who are candidates for conservative therapy must be extensively counseled regarding the risks and must comply with close surveillance.     

Fertility after conservative treatment for borderline ovarian tumors: a French multicenter study

OBJECTIVE: To examine fertility outcomes and determinants of fertility after conservative surgery for women with borderline ovarian tumors. DESIGN: Retrospective multicenter study. SETTING: Thirteen specialized gynecologic units and one cancer center. PATIENT(S): In a study of women with borderline ovarian tumors, 162 of 360 women underwent conservative surgery; from these 162, we compared epidemiologic, surgical, and histological parameters between 21 women who conceived and 44 women who failed to conceive. INTERVENTION(S): Conservative surgery for borderline ovarian tumors. MAIN OUTCOME MEASURE(S): Fertility results and outcome. RESULT(S): Women undergoing conservative treatment were significantly younger and more likely to be nulliparous. Tumor size was significantly smaller in the conservative treatment group. Thirty pregnancies occurred in 21 (32.3%) of the 65 women who wished to conceive after conservative treatment. Twenty-seven pregnancies were spontaneous, whereas three occurred after ovarian stimulation and IUI (one case) or IVF (2 cases). Women who conceived did not differ from women who did not conceive in terms of the tumor recurrence rate or the mean time to recurrence (39.6 +/- 28.2 and 22.9 +/- 14.9 months, respectively). Age at initial treatment was the only determinant of fertility. CONCLUSION(S): Despite a high recurrence rate, our results confirm that conservative surgery for women with borderline ovarian tumors is an acceptable option and that fertility is preserved in nearly one third of cases.     

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.     

Effects of Cancer Treatment on Reproduction and Fertility

Objective: (1) To review the effects of cancer treatment on reproduction and fertility in both women and men and (2) to review current and new techniques that could be used to preserve fertility and hormone production in women who have undergone cancer treatment.Data Sources: Entries to MEDLINE and CANCERLIT through to October 2001 were searched for evidence relevant to this article.Methods of Study Selection: This document is primarily based on large retrospective cohort series and case reports, as no randomized trials were available.Tabulation, Integration, and Results: The first part of this review article focuses on the effects of radiation and chemotherapy on reproductive function and innovative medical and surgical techniques employed to minimize these effects. The second part of this article describes conservative methods of managing cervical, endometrial, and ovarian cancer for women who wish to preserve their fertility.Conclusions: Over the last decade, there has been a trend toward trying to preserve reproductive function in young patients with malignancy. Information acquired over the last century on the reproductive effects of radiation and chemotherapy has enabled us to tailor our treatment of various malignancies affecting young patients. As we learn more about the biology and clinical behaviour of gynaecologic malignancies, we are able to modify surgical management to preserve fertility in select cases. All of these trends are in keeping with our goal to optimize quality of life in cancer care without compromising safety or survival.     

Fertility-sparing Surgery for Patients with Cervical,Endometrial, and Ovarian Cancers

ObjectiveNearly 10% of the 1.3 million women living with a gynecologic cancer are aged <50 years. For these women, although their cancer treatment can be lifesaving, it's also life-altering because traditional surgical procedures can cause infertility and, in many cases, induce surgical menopause. For appropriately selected patients, fertility-sparing options can reduce the reproductive impact of lifesaving cancer treatments. This review will highlight existing recommendations as well as innovative research for fertility-sparing treatment in the 3 major gynecologic cancers.Tabulation, Integration, and ResultsFor early-stage cervical cancers, fertility-sparing surgeries include cold knife conization, simple hysterectomy with ovarian preservation, or radical trachelectomy with placement of a permanent cerclage. In locally advanced cervical cancer, ovarian transposition before radiation therapy can help preserve ovarian function. For endometrial cancers, fertility-sparing treatment includes progestin therapy with endometrial sampling every 3 to 6 months. After cancer regression, progestin therapy can be halted to allow attempts to conceive. Hysterectomy with ovarian preservation can also be considered, allowing for fertility using assisted reproductive technology and a gestational carrier. For ovarian cancers, fertility-sparing surgery includes unilateral salpingo-oophorectomy or bilateral salpingo-oophorectomy (with lymphadenectomy and staging depending on tumor histology). With higher-risk histology or higher early-stage disease, adjuvant chemotherapy is recommended—however, this carries a 3% to 10% risk of ovarian failure. Use of oocyte or embryo cryopreservation in patients with early-stage ovarian malignancy remains an area of ongoing research.ConclusionOverall, fertility-sparing management of gynecologic cancers is associated with acceptable rates of progression-free survival and overall survival and is less life-altering than more radical surgical approaches.     

Multiple primary malignancies in patients with gynecologic cancer

A retrospective analysis was made of 1044 patients with gynecologic malignancies treated in our department over a 12-year period, in order to review the frequency and types of multiple primary neoplasms. Multiple primary neoplasms were detected in 45 (4.3%) cases, including 16 (2.1%) out of 733 cervical cancers, 14 (8.2%) out of 166 endometrial cancers, three (15%) out of 20 vaginal cancers and 12 (9.8%) out of 123 ovarian cancers. Fifteen cases were synchronous and the remaining 24 cases were heterochronous, with an average 4.9-year interval. The most frequent other site of neoplasm was the breast, particularly in patients with endometrial or ovarian cancer. We conclude that gynecologic malignancies are often associated with primary cancers elsewhere, especially in the breast, stomach, colon and thyroid. A patient presenting with a gynecologic malignancy should be thoroughly examined for a second cancer, as should patients being followed-up after treatment for genital tract cancer.     

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.     

Menstrual function and childbearing potential after fertility-sparing surgery and platinum-based chemotherapy for malignant ovarian germ cell tumours

Malignant ovarian germ cell tumours (MOGCT) account for 5% of all ovarian malignancies. Their elevated chemosensitivity, the frequent unilaterality and the young age of patients have strongly supported the conservative surgery as the standard approach, often followed by adjuvant platinum-based chemotherapy. The risk for recurrence is not affected by the performance of conservative versus radical surgery. During chemotherapy 50% of patients become amenorrhoeic but more than 95% of them resume normal menses after treatment completion. Literature has reported several healthy babies born after fertility-sparing surgery with or without chemotherapy for MOGCT. The incidence of miscarriages is in the normal range, whereas malformation rate is slightly higher compared to general population, without any difference between chemotherapy-treated and -untreated patients. Therefore, young women with MOGCT must be reassured of their excellent chances of survival and fertility preservation following conservative surgery and adjuvant platinum-based chemotherapy.     

Paraaortic lymphadenectomy in gynecological tumors

The purpose of this Study was to determine role of para-aortic lymphadenectomy in patients with gynecologic malignancies. In review literature the authors reports was to show role of paraaortic lymphadenectomy in surgical staging and the most important role in treatment plan. The results confirm the diagnostic and prognostic value of paraaortic lymphadenectomy in patients with endometrial carcinoma, cervical cancer and ovarian cancer and adjuvant treatment after primary surgical procedure. The authors affirm that lymph nodes metastases represent the most reliable markers of high risk patients. The position about therapeutic role of paraaortic lymphadenectomy remains controversial.     

Radiographic imaging in gynecologic oncology.

Current radiographic techniques are useful for evaluating and managing patients with gynecologic malignancies. Lymphoscintigraphy may prove useful in limiting surgery in women with vulvar cancer who have negative sentinel groin nodes. Selected patients benefit from pretherapy MRI scanning to help determine treatment of cervical or endometrial malignancies. Sonographic techniques are helpful in discriminating benign from malignant adnexal or pelvic masses, and preoperative CT scans are helpful in determining the extent of advanced ovarian cancer. The FDG PET scans appear to help localize occult disease in patients with a variety of gynecologic malignancies. Further refinements of currently available techniques or newer techniques, however, are needed to increase the sensitivity for detection of subclinical or microscopic metastases in patients with gynecologic malignancies.     

Successful pregnancy after conservative surgery for stage IC ovarian cancer with serous borderline tumor on controlateral ovary: a case report

BACKGROUND: In invasive ovarian cancer, fertility saving surgery is confined to early-stage and low-grade disease, and only few study reported sparing fertility up to FIGO stage IC ovarian cancer. CASE: We present a rare case of a 30-year-old woman affected by IC ovarian cancer with borderline tumor on controlateral ovary who underwent "conservative" debulking surgery followed by adjuvant chemotherapy. A spontaneous planned pregnancy occurred 5 years postsurgery. At 60-month follow-up, patients have no evidence of disease. CONCLUSIONS: Nowadays, preservation of ovarian function in women with tumors in early stage should be evaluated for conservative surgery. It is important to emphasize that patients selected for conservative surgery should have complete surgical staging. Careful follow-up is mandatory to ensure safety of this procedure.     

The use of colorectal stents for palliation of large-bowel obstruction due to recurrent gynecologic cancer

OBJECTIVE: Acute large-bowel obstruction (LBO) is considered a surgical emergency. In gynecologic oncology patients with LBO due to recurrent tumor, surgery has been the standard treatment. However, operative intervention has significant associated morbidity and mortality. Recent reports have addressed the use of colorectal stents for the treatment of colonic malignancies. We are reporting our experience with colorectal stents in gynecologic oncology patients. METHODS: We reviewed the records of all patients who underwent colorectal stent placement for palliation of LBO due to recurrent gynecologic malignancy from August 2001 to January 2003. RESULTS: Six patients were identified; five patients had recurrent ovarian cancer and one had recurrent endometrial cancer. The mean age of the six patients at the time of stent placement was 51.5 years (range, 22-83 years).The length of LBO ranged from 2 to 10 cm. Two patients had a lumen of 1 to 2 mm before stent placement, while the other four had a complete obstruction and needed balloon dilatation before the deployment of the stent. Four (67%) of six patients had immediate relief, with passage of stool and flatus noted at the time of the colorectal stent placement. Stent placement failed to relieve the LBO in two patients (33%); these patients went on to receive colostomies. Of the four patients who had successful stent placement, the mean survival after stent placement was 120 days. One patient had a contained sigmoid bowel perforation noted 12 days after stent placement, which resolved with conservative measures. CONCLUSION: Colonic stents appear to be a useful option in the management of patients with LBO due to recurrent gynecologic malignancy.     

妇科恶性肿瘤保留生育功能肿瘤结局

子宫颈癌、卵巢癌和子宫内膜癌是妇科常见的恶性肿瘤，近年发病有年轻化趋势。对于有生育要求的年轻患者，如何在不增加肿瘤风险的情况下，保留患者术后的生育功能，成为近年来备受关注的问题。文章对保留生育功能的妇科恶性肿瘤患者的肿瘤结局进行阐述。     

Fertility and recurrence results of conservative surgery for borderline ovarian tumors

OBJECTIVES: To evaluate the fertility and recurrence outcomes in women treated with fertility-sparing surgery for borderline ovarian tumors. METHODS: A total of 142 patients with borderline ovarian tumors managed surgically from 1993 to 2004 were identified from gynecologic oncology and pathology files of SSK Ankara Maternity and Women's Health Teaching Hospital. Sixty-two of those patients who had conservative surgery were eligible for the study. Information was acquired by retrospective medical record review and patient interview. RESULTS: The observed recurrence rates after radical and fertility-sparing surgery were 0.0% and 6.5%, respectively. Four patients from the conservative surgery group developed recurrence, in contrast to none of the patients from the non-conservative surgery group. No disease-related deaths occurred in any group. In the conservatively managed group, ten women had successful pregnancies, with a total of 10 live births and 3 abortions. The mean duration of follow-up for the conservative surgery group was 44.3 months (range, 3-128). CONCLUSION: Fertility-sparing surgery for borderline ovarian tumors should be considered for women in the reproductive age group who desire preservation of fertility. Recurrence is noted significantly more often after this type of treatment and close follow-up is needed to detect recurrent disease.