Fertility Preservation in Gynecologic Cancers PDF

FERTILITY SPARING THERAPIES IN GYNOCOLOGIC CANCERS ZIYA KALEM,MD ISTINYE UNIVERSITY FACULTY OF MEDICINE  LEARNING OBJECTIVES PATIENT SELECTION FERTILITY PRESERVING APPROACHES In recent years, advances in cancer treatment have significantly extended life expectancy. As a result, fertility...

FERTILITY SPARING THERAPIES IN GYNOCOLOGIC CANCERS ZIYA KALEM,MD ISTINYE UNIVERSITY FACULTY OF MEDICINE  LEARNING OBJECTIVES PATIENT SELECTION FERTILITY PRESERVING APPROACHES In recent years, advances in cancer treatment have significantly extended life expectancy. As a result, fertility-preserving approaches have gained importance as the possibility of childbearing in young patients comes to the agenda. Invasive Cervical Cancer Conservative management of early staged cervical cancer in young women should be considered if childbearing is important to that patient. Stage Ia1 cancers are those with stromal invasion up to 3 mm in depth and no greater than 7 mm. Stage Ia2 are when invasion is present at 3 to 5 mm in depth and no greater than 7 mm.  Patients with FIGO stage Ia1 and SGO criteria for microinvasion could be treated conservatively with simple hysterectomy, or if continued fertility is desired conization only, provided surgical margins are free of cancer. In addition, patients with FIGO stage Ib lesions smaller than 2 cm with limited endocervical involvement and no pathologic evidence of lymph node metastases may be candidates for radical trachelectomy. Adnexal Masses Operative treatment has traditionally been the mainstay of management in ovarian carcinoma Because 3% to 17% of patients with ovarian cancer are younger than 40 years of age, some patients may consider options for fertility preservation in the setting of an adnexal mass. Conservative therapy, designed by preservation of some ovarian tissue, appears to be safe, although no prospective trials have compared conservative surgery with bilateral salpingooophorectomy. Germ Cell, Stromal, and Other Ovarian Tumors Because 85% of all patients with dysgerminomas are younger than 30 years, conservative therapy and preservation of fertility are major considerations In select cases such as stage Ia dysgerminoma and stage Ia grade I immature teratoma, unilateral salpingooophorectomy is thought to be curative and is all that is required. Epithelial Ovarian Cancer In the young woman with stage IA disease who is desirous of further childbearing, unilateral salpingo-oophorectomy may be associated with minimal increased risk of recurrence Conservative surgery is generally not recommended for patients with clear cell or carcinosarcoma or grade III tumors and when disease is present outside the ovaries The excellent response of germ cell malignancies to adjuvant chemotherapy has allowed a tailored approach to the surgical management of this disease in women desiring fertility preservation. Although unilateral salpingo-oophorectomy should be considered the standard procedure in such cases, recently, some clinicians have advocated ovarian cystectomy in select cases of immature teratoma. Cancer in Pregnancy Management of vulvar cancer in pregnancy. Invasive vulvar malignant disease diagnosed during the first, second, and early third trimesters is usually treated as indicated in nonpregnant patients some time after the 18th week of pregnancy. Women treated during pregnancy may be allowed to attempt vaginal delivery provided the vulvar wounds are well healed and there are no indications for additional therapy. Cancer in Pregnancy Primary Invasive Vaginal Tumors The pregnancy should be disregarded if the diagnosis is made in the first or early second trimester. If the pregnancy is further along, the decision for appropriate time of intervention depends on the preferences of the patient and the oncologist. Cancer in Pregnancy Endometrial Cancer Endometrial carcinoma in conjunction with pregnancy is extremely rare. The recommended therapy for endometrioid adenocarcinomas associated with pregnancy is total hysterectomy with bilateral salpingo- oophorectomy and adjuvant radiotherapy when indicated. Cancer in Pregnancy Fallopian Tube Cancer In most instances, the diagnosis is established at laparotomy, and the treatment is total abdominal hysterectomy with bilateral salpingo- oophorectomy and postoperative radiotherapy or chemotherapy The criteria through which surgeons determine candidacy for fertility preservation must be carefully devised and rigorously adhered to. Cancer in Pregnancy Complete Hydatidiform Mole With Coexistent Fetus After fetal anomalies and an abnormal karyotype are excluded, with some degree of caution, the literature supports continuing the pregnancy provided there is no evidence of preeclampsia and the pregnant woman strongly wishes to do so The major role of primary hysterectomy should be as part of primary treatment for women with low-risk nonmetastatic GTN and no desire for future fertility. Growing evidence for the efficacy and safety of female gamete vitrification has led both the American Society for Reproductive Medicine and the European Society for Human Reproduction and Embryology to not consider this technique to be experimental IN RECENT YEARS,WE HAVE BEEN RECOMMENDİNG OOCYTE FREEZING TO OUR PATIENT WITH MALIGNANT TUMORS Key Recommendations Discuss fertility preservation with all patients of reproductive age (and with parents or guardians of children and adolescents) if infertility is a potential risk of therapy Refer patients who express an interest in fertility preservation (and patients who are ambivalent) to reproductive specialists Address fertility preservation as early as possible, before treatment starts Document fertility preservation discussions in the medical record Answer basic questions about whether fertility preservation may have an impact on successful cancer treatment Refer patients to psychosocial providers if they experience distress about potential infertility Encourage patients to participate in registries and clinical studies  Adult Females Present both embryo and oocyte cryopreservation as established fertility preservation methods Discuss the option of ovarian transposition (oophoropexy) when pelvic radiation therapy is performed as cancer treatment Inform patients of conservative gynecologic surgery and radiation therapy options Inform patients that there is insufficient evidence regarding the effectiveness of ovarian suppression (gonadotropin-releasing hormone analogs) as a fertility preservation method, and these agents should not be relied on to preserve fertility Inform patients that other methods (eg, ovarian tissue cryopreservation, which does not require sexual maturity, for the purpose of future transplantation) are still experimental  Children Use established methods of fertility preservation (semen cryopreservation and oocyte cyropreservation) for postpubertal minor children, with patient assent, if appropriate, and parent or guardian consent Present information on additional methods that are available for children but are still investigational Refer for experimental protocols when available  The effect of cancer treatment on the ovary (chemotherapy and radiotherapy) follicle depletion stromal fibrosis vascular injury Survivors in whom ovarian function resumes or is maintained after cancer treatment might face a shortened window of fertility.  The extent of the damage to the ovary depends on the type and dose of chemotherapy the radiotherapy dose fractionation scheme irradiation field the ovarian reserve before treatment  Fertility preservation approaches depend on patient age cancer type type of treatment presence of a male partner patient preference for the use of banked donor sperm time available for fertility preservation intervention the likelihood of ovarian metastasis  Fertility preservation methods oocyte and embryo cryopreservation ovarian transposition (oophoropexy) Ovarian suppression with gonadotropin- releasing hormone analogues during adjuvant chemotherapy (hypothetical) Ovarian cortex cryopreservation (experimental)  Delay ? No published randomised controlled trials have investigated the association between a delay in chemotherapy and survival in patients with breast cancer. seven independent studies that investigated overall survival in patients with operable primary breast cancer who received cyclophosphamide, methotrexate, and fluorouracil and anthracycline- based regimens suggested that overall survival decreased by 15% for every 4-week delay in initiation of chemotherapy Yu K-D, Huang S,2013 What can be done to avoid the delay of chemotherapy? Oocyte in-vitro maturation ovarian cortex transplantation Cryopreservation of ovarian tissue Primordial and preantral follicle culture Lancet. Author manuscript; available in PMC 2015 October 04.  Emerging technologies Ovarian follicle culture in vitro Ovarian follicle transplantation (artificial ovary) Oogonial stem cells In vitro activation of ovarian follicles Administration of drugs for Specific target tissues Use of nanoparticles Use of fertoprotective reagents  Existing technologies 1. Embryo cryopreservation 2. Oocyte cryopreservation a)Mature oocyte cryopreservation b)Immature oocyte cryopreservation and in vitro maturation 3.Ovarian stimulation protocols used for embryo or mature oocyte cryopreservation a) Random-start COS b)The use aromatase inhibitors or tamoxifen in patients with hormone-sensitive cancer 4.Ovarian tissue cryopreservation a) Cryopreservation of ovarian cortical tissue b)Cryopreservation of whole ovary c)Aspiration of immature oocytes during ovarian tissue cryopreservation 5.Fertoprotective adjuvant therapy Gonadotropinreleasing hormone (GnRH) agonists have been used during chemotherapy as a way to reduce the toxic effects of cancer treatment on growing ovarian follicles and their enclosed oocytes.