Kenny A. Rodriguez-Wallberg

GnRH agonist trigger for women with breast cancer undergoing fertility preservation by aromatase inhibitor/FSH stimulation

Aromatase inhibitors can be utilized to minimize oestrogen exposure in breast cancer patients undergoing gonadotrophin stimulation. This retrospective-prospective study determined whether using a gonadotrophin-releasing hormone agonist (GnRHa) trigger instead of human chorionic gonadotrophin (HCG) would reduce oestrogen exposure and improve cycle outcomes in aromatase inhibitor cycles. Seventy-four breast cancer patients who desired fertility preservation, with normal ovarian reserve and < 45 years of age received letrozole 5mg/day plus recombinant FSH 150-300 IU/day for ovarian stimulation. Subjects either received HCG 5000-10,000 IU (n=47) or leuprolide acetate 1mg (GnRHa, n=27) as trigger. Oestradiol measurements were repeated 4 days after the trigger and subjects were evaluated for ovarian hyperstimulation syndrome (OHSS). In the GnRHa group, oestradiol concentrations dropped significantly after the trigger than the HCG group (P=0.013) and there was a lower incidence of OHSS. GnRHa trigger resulted in a higher number and percentage of mature oocytes and a higher number of cryopreserved embryos or oocytes compared with HCG. GnRHa trigger improves outcomes by increasing the yield of mature oocytes and embryos in aromatase inhibitor cycles and also decreases the post-trigger oestradiol exposure as well as OHSS risks in women with breast cancer.

PSYCHOSOCIAL DISTRESS IN YOUNG CANCER SURVIVORS

OBJECTIVES To review existing literature about the psychosocial reactions of cancer patients and provide information about the needs of patients wishing to preserve fertility. DATA SOURCES Journal articles, research studies. CONCLUSION The desire for biological parenthood is an important issue for cancer survivors. Patients may not receive accurate, timely information about fertility-sparing options; those not receiving this information are at increased risk for psychological distress. IMPLICATIONS FOR NURSING PRACTICE Fertility-preservation decisions are complex and a team approach may identify patients at risk for psychological distress and provide opportunities for discussion of psychosocial issues involved. Nurses must be informed about the emotional reactions and informational needs of their patients.

Fertility preservation in women with breast cancer.

Fertility preservation is an important issue for young women diagnosed with breast cancer. The most well-established options for fertility preservation in cancer patients, embryo and oocyte cryopreservation, have not been traditionally offered to breast cancer patients as estradiol rise during standard stimulation protocols may not be safe for those patients. Potentially safer stimulation protocols using tamoxifen and aromatase inhibitors induce lower levels of estradiol whereas similar results in terms of number of oocyte and embryo obtained to standard protocols. Cryopreservation of immature oocytes and ovarian cortical tissue, both still experimental methods, are also fertility preservation options for breast cancer patients.

Options on fertility preservation in female cancer patients

Infertility following treatment of cancer is a quality of survivals recognized issue and efforts should be made to help young cancer patients retaining their fertility potential. Options to preserve fertility in female patients include well established methods such as shielding to reduce radiation damage to reproductive organs, fertility-sparing surgery and emergency in vitro fertilization after controlled ovarian stimulation, aiming at freezing embryos. Transfer of frozen/thawed embryos today is a clinical routine in fertility clinics worldwide and it has been used for over 25 years. Mature oocytes after ovarian stimulation can also be frozen unfertilized, nevertheless overall pregnancy rates after fertilization of frozen-thawn oocytes are still relatively lower than those with embryo freezing. Remaining fertility preservation options are still in development and include the freezing of immature oocytes aiming at later in vitro maturing and fertilizing them and the cryopreservation of ovarian tissue for future retransplantation or for in vitro growth and maturation of follicles, both still experimental.

Four spontaneous pregnancies and three live births following subcutaneous transplantation of frozen banked ovarian tissue: What is the explanation?

OBJECTIVE To report the long-term follow-up of an experimental heterotopic ovarian transplantation with frozen-thawed ovarian tissue. DESIGN Long-term follow-up of an experimental surgery; case report. SETTING Academic reproductive medicine center. PATIENT(S) A 28-year-old cancer survivor with previous Hodgkin disease and relapse. INTERVENTION(S) Laparoscopic oophorectomy for ovarian cryopreservation before preconditioning chemotherapy for hematologic stem cell transplantation. Ovarian tissue thawing and subcutaneous heterotopic ovarian transplantation in the lower abdominal wall 2½ years after the hematologic stem cell transplantation. MAIN OUTCOME MEASURE(S) Resumption of ovarian function after transplantation, recovery of fertility, and pregnancy outcome. RESULT(S) Follicle development was observed in the graft 2 months after transplantation, and a P value of 14 ng/mL indicated ovulation. The patient conceived spontaneously four times within 5 years and delivered three children. The in situ ovary remained atrophic but showed occasional follicle activity contemporaneously with the graft. CONCLUSION(S) The mechanism behind spontaneous restoration of fertility with consecutive viable pregnancies after a heterotopic ovarian transplantation needs to be explored. Further laboratory and clinical research will be needed to explore the true origin of pregnancies after ovarian transplantations.

Fertility preservation during cancer treatment: clinical guidelines.

The majority of children, adolescents, and young adults diagnosed with cancer today will become long-term survivors. The threat to fertility that cancer treatments pose to young patients cannot be prevented in many cases, and thus research into methods for fertility preservation is developing, aiming at offering cancer patients the ability to have biologically related children in the future. This paper discusses the current status of fertility preservation methods when infertility risks are related to surgical oncologic treatments, radiation therapy, or chemotherapy. Several scientific groups and societies have developed consensus documents and guidelines for fertility preservation. Decisions about fertility and imminent potentially gonadotoxic therapies must be made rapidly. Timely and complete information on the impact of cancer treatment on fertility and fertility preservation options should be presented to all patients when a cancer treatment is planned.

Fertility Preservation and Pregnancy in Women With and Without BRCA Mutation–Positive Breast Cancer

Women with breast cancer face many challenges when considering fertility preservation. Delayed referral results in the limitation of fertility preservation options because most established methods, such as embryo and oocyte cryopreservation, require several weeks to complete. Women with BRCA mutations, on the other hand, may be more aware of fertility issues and motivated to see fertility preservation specialists earlier. Fear of exposure to estrogen limits access to fertility preservation via embryo or oocyte cryopreservation; however, the use of aromatase inhibitors as ovarian stimulants reduces such concern. Ovarian cryopreservation can be used when there is insufficient time to perform ovarian stimulation because this technique does not require hormonal stimulation, but there are safety concerns both in women with BRCA mutations and in patients with hormone receptor-positive disease as well. There does not seem to be a proven ovarian suppression strategy to preserve fertility in women with breast cancer. Pregnancy appears to be safe for breast cancer survivors but studies specific for women with BRCA mutations are lacking. Women with BRCA mutations may elect to use preimplantation genetic diagnosis during in vitro fertilization to avoid transmitting the mutation, but there may be psychosocial difficulties in entertaining this option. Overall, the last decade has brought many options for women with breast cancer considering fertility preservation, but numerous challenges remain. The presence of BRCA mutations further contributes to these challenges.

In vitro maturation improves oocyte or embryo cryopreservation outcome in breast cancer patients undergoing ovarian stimulation for fertility preservation.

This study tested in-vitro maturation (IVM) as a complementary strategy to improve the mature oocyte yield of breast cancer patients undergoing ovarian stimulation for fertility preservation. Secondary analysis of prospectively collected data is performed for 32 breast cancer patients undergoing oocyte or embryo cryopreservation before chemotherapy. Total number of oocytes and/or embryos cryopreserved following IVM is compared with the total number cryopreserved before IVM. Overall, 464 oocytes were retrieved, of which 274 were mature. Following IVM, the number of total mature oocytes increased to 399 (45% increase in mature oocyte yield, P<0.0001). Fertilization rate after IVM was statistically significantly higher than the fertilization of already mature oocytes at retrieval (86% versus 73%, respectively, P<0.05). The total number of oocytes and embryos frozen before IVM was 207 (45% of all oocytes retrieved). This number increased to 320 (69% of all oocytes retrieved) following IVM (P<0.0001). IVM is a useful strategy to improve the mature oocyte yield of fertility preservation cycles. Immature oocytes retrieved during oocyte/embryo cryopreservation cycles should not be discarded to improve the future potential of fertility.

Fertility preservation by ovarian stimulation and oocyte cryopreservation in a 14-year-old adolescent with Turner syndrome mosaicism and impending premature ovarian failure.

OBJECTIVE To report a novel approach to fertility preservation in adolescents with Turner syndrome mosaicism by repeated controlled ovarian stimulation and oocyte cryopreservation. DESIGN Case report. SETTING Academic reproductive medicine center. PATIENT(S) Fourteen-year-old adolescent diagnosed with Turner syndrome mosaicism. INTERVENTION(S) Two cyles of controlled ovarian stimulation and oocyte cryopreservation within 1 year. MAIN OUTCOME MEASURE(S) Recovery of oocytes after controlled ovarian stimulation and oocyte cryopreservation. RESULT(S) Eleven oocytes were retrieved, of which eight were mature and three were immature during the first cycle. One year later, four mature and three immature oocytes were retrieved after a treatment cycle with even higher gonadotropin doses. All oocytes were cryopreserved by vitrification. CONCLUSION(S) Controlled ovarian stimulation and oocyte cryopreservation may be an option for fertility preservation in selected adolescents with Turner syndrome mosaicism and impending ovarian failure.

Women more vulnerable than men when facing risk for treatment-induced infertility: A qualitative study of young adults newly diagnosed with cancer

Abstract Background. Being diagnosed with cancer constitutes not only an immediate threat to health, but cancer treatments may also have a negative impact on fertility. Retrospective studies show that many survivors regret not having received fertility-related information and being offered fertility preservation at time of diagnosis. This qualitative study investigates newly diagnosed cancer patients’ experiences of fertility-related communication and how they reason about the risk of future infertility. Material and methods. Informants were recruited at three cancer wards at a university hospital. Eleven women and 10 men newly diagnosed with cancer participated in individual semi-structured interviews focusing on three domains: experiences of fertility-related communication, decision-making concerning fertility preservation, and thoughts and feelings about the risk of possible infertility. Data was analyzed through qualitative content analysis. Results. The analysis resulted in three sub-themes, ‘Getting to know’, ‘Reacting to the risk’ and ‘Handling uncertainty’, and one main theme ‘Women more vulnerable when facing risk for infertility’, indicating that women reported more negative experiences related to patient-provider communication regarding fertility-related aspects of cancer treatment, as well as negative emotional reactions to the risk of infertility and challenges related to handling uncertainty regarding future fertility. The informants described distress when receiving treatment with possible impact on fertility and used different strategies to handle the risk for infertility, such as relying on fertility preservation or thinking of alternative ways to achieve parenthood. The negative experiences reported by the female informants may be related to the fact that none of the women, but almost all men, had received information about and used fertility preservation. Conclusions. Women newly diagnosed with cancer seem to be especially vulnerable when facing risk for treatment-induced infertility. Lack of shared decision-making concerning future fertility may cause distress and it is therefore necessary to improve the fertility-related communication targeted to female cancer patients.