Faculty Bibliography

OBJECTIVE:To describe a technique of fertility preservation by ovarian transposition combined with ovarian cryopreservation in the setting of oncologic pelvic radiation for a reproductive age woman. DESIGN/METHODS:Case report. SETTING/METHODS:IVF center at a tertiary care hospital. PATIENT(S)/METHODS:Thirty-year-old nulligravid women who previously underwent lumbar spinal cord tumor debulking requested fertility preservation before pelvic radiation. INTERVENTION(S)/METHODS:Laparoscopic ovarian transposition with cryopreservation of the contralateral ovary. MAIN OUTCOME MEASURE(S)/METHODS:New technique in fertility preservation. RESULT(S)/RESULTS:Laparoscopic surgery was used to evaluate, select, and remove a single ovary that then underwent cryopreservation. Transposition of the remaining ovary was subsequently successfully performed, placing it of out of the pelvis. CONCLUSION(S)/CONCLUSIONS:The combination of ovarian cryopreservation and ovarian transposition may maximize future fertility options for women facing pelvic irradiation. This combined approach should be included among the options offered to reproductive age women before pelvic radiation.

CONTEXT/BACKGROUND:Women with breast cancer are not typically offered embryo or oocyte cryopreservation to preserve their fertility before chemotherapy because of the potential risks associated with high estrogen levels arising from ovarian stimulation. OBJECTIVE:We aimed to determine whether the combination of an aromatase inhibitor with gonadotropin treatment in breast cancer patients produces comparable results to standard in vitro fertilization (IVF), without a significant increase in estradiol levels and delay in the initiation of chemotherapy. PATIENTS AND METHODS/METHODS:Stages I-IIIA breast cancer patients (n = 47) received 5 mg/d letrozole and 150-300 IU FSH to cryopreserve embryos or oocytes. Age-matched retrospective controls (n = 56) were selected from women who underwent IVF for tubal disease. RESULTS:Whereas letrozole and FSH stimulation resulted in significantly lower peak estradiol levels (mean +/- sd 483.4 +/- 278.9 vs. 1464.6 +/- 644.9 pg/ml; P < 0.001) and 44% reduction in gonadotropin requirement, compared with controls, the length of stimulation, number of embryos obtained, and fertilization rates were similar. The human chorionic gonadotropin administration criteria had to be adjusted to 20 mm after letrozole stimulation, compared with 17-18 mm in the controls. The mean delay from surgery to cryopreservation was 38.6 d, with 81% of all patients completing their IVF cycles within 8 wk of surgery. CONCLUSION/CONCLUSIONS:Ovarian stimulation with letrozole and FSH appears to be a cost-effective alternative for fertility preservation in breast cancer patients with reduced estrogen exposure, compared with standard IVF. If patients are referred promptly, they may undergo embryo or oocyte cryopreservation without a delay in chemotherapy.

OBJECTIVE:To determine the efficiency of oocyte cryopreservation relative to IVF with unfrozen oocytes. DESIGN/METHODS:Meta-analysis. SETTING/METHODS:Academic assisted reproduction center. PATIENT(S)/METHODS:Results of all reports from January 1997 to June 2005 with the patients undergoing IVF-intracytoplasmic sperm injection (ICSI) with cryopreserved cycles between 1996 and 2004 were compared with those of patients who underwent IVF-ICSI with unfrozen oocytes in 2002 and 2003 in our program. INTERVENTION(S)/METHODS:Mean age and number of ET cycles originating from unfrozen oocytes was matched with those for thaw cycles originating from oocytes cryopreserved with a slow-freezing (SF) protocol. Vitrification (VF) reports were not included in the comparative analysis because of a small number of pregnancies (10) before June 2005. MAIN OUTCOME MEASURE(S)/METHODS:The comparison of fertilization rate, clinical pregnancy, and live-birth rates per injected oocyte, clinical pregnancy and live-birth rates per transfer, and implantation rate between IVF-ICSI cycles with frozen and unfrozen oocytes. RESULT(S)/RESULTS:Live-birth rates per oocyte thawed were 1.9% and 2.0% for SF and VF, respectively, before June 2005. Live-birth rates per injected oocyte and ET, respectively, were 3.4% and 21.6% for SF and were 6.6% and 60.4% for IVF with unfrozen oocytes. Compared to women who underwent IVF after SF, IVF with unfrozen oocytes resulted in significantly better rates of fertilization (odds ratio [95% confidence interval]); 2.22 (1.80, 2.74), of live birth per injected oocyte; 1.5 (1.26, 1.79), and of implantation; 4.66 (3.93, 5.52). These odds ratios were lower when oocyte cryopreservation success rates from 2002-2004 were compared with those for IVF with unfrozen oocytes. When the reports after June 2005 were considered, this trend did not appear to continue. With the consideration of VF reports after June 2005, however, higher pregnancy rates were achieved. CONCLUSION(S)/CONCLUSIONS:In vitro fertilization success rates with slow-frozen oocytes are significantly lower when compared with the case of IVF with unfrozen oocytes. Although oocyte cryopreservation with the SF method appears to be justified for preserving fertility when a medical indication exists, its value for elective applications remains to be determined. Pregnancy rates with VF appear to have improved, but further studies will be needed to determine the efficiency and safety of this technique.

PURPOSE/OBJECTIVE:To develop guidance to practicing oncologists about available fertility preservation methods and related issues in people treated for cancer. METHODS:An expert panel and a writing committee were formed. The questions to be addressed by the guideline were determined, and a systematic review of the literature from 1987 to 2005 was performed, and included a search of online databases and consultation with content experts. RESULTS:The literature review found many cohort studies, case series, and case reports, but relatively few randomized or definitive trials examining the success and impact of fertility preservation methods in people with cancer. Fertility preservation methods are used infrequently in people with cancer. RECOMMENDATIONS/CONCLUSIONS:As part of education and informed consent before cancer therapy, oncologists should address the possibility of infertility with patients treated during their reproductive years and be prepared to discuss possible fertility preservation options or refer appropriate and interested patients to reproductive specialists. Clinician judgment should be employed in the timing of raising this issue, but discussion at the earliest possible opportunity is encouraged. Sperm and embryo cryopreservation are considered standard practice and are widely available; other available fertility preservation methods should be considered investigational and be performed in centers with the necessary expertise. CONCLUSION/CONCLUSIONS:Fertility preservation is often possible in people undergoing treatment for cancer. To preserve the full range of options, fertility preservation approaches should be considered as early as possible during treatment planning.

Ovarian cryopreservation and transplantation is an emerging technology to preserve fertility in women and children undergoing cancer treatment. Recent reports of live births after orthotopic transplantation raised hopes for the future success of this procedure. However, doubts remained whether the reported pregnancies were as a result of resumed function in the remaining ovary. We recently performed an autologous heterotopic ovarian transplantation in a 32-year-old Hodgkin lymphoma survivor who was menopausal for 2.5 years as a result of a preconditioning chemotherapy given before a hematopoietic stem cell transplant. Subsequent to the transplantation, the patient conceived twice within 3 months and delivered a healthy female child at 40 weeks of gestation. The occurrence of spontaneous pregnancies after heterotopic ovarian transplantation highlights the need for caution when interpreting the source of pregnancies in recipients with intact ovaries. On the other hand, the temporal relationship between the ovarian transplant and the spontaneous resumption of ovarian function and pregnancies in previously menopausal women is intriguing, especially in the light of recent reports of germ cell renewal and migration from the bone marrow to the ovary in rodents.

Breast cancer accounts for one third of all neoplasms seen in reproductive-age women and affects tens of thousands of women each year in that age group. The adjuvant chemotherapy regimens used for the treatment commonly affect fertility and cause premature ovarian failure. There have been recent advances in the field of fertility preservation, which can allow many of these breast cancer survivors to have children in the future. The most established option is embryo cryopreservation; oocyte cryopreservation can be considered in single women. Both of these approaches require approximately 2 weeks of ovarian stimulation beginning with the onset of the patient's menstrual cycle. Thus, it is crucial that these patients are referred to appropriate assisted reproduction centers as soon as they are diagnosed with breast cancer. Recently developed ovarian stimulation protocols using tamoxifen and letrozole can be used to increase the margin of safety in these patients. When and if a breast cancer patient does not have time to undergo ovarian stimulation prior to chemotherapy, ovarian cryopreservation for future autotransplantation can be offered as the last resort. The benefit of ovarian protection by gonadotropin-releasing hormone analogues is unproven and unlikely, and thus this treatment should not be offered as the sole method of fertility preservation.

An increasing number of women have been subjected to cytotoxic chemoradiotherapy for various malignant and nonmalignant diseases. Women who face the possibility of premature or imminent ovarian failure caused by cytotoxic therapy may retain their fertility potential with ovarian tissue cryopreservation. Until recently, this technique could only be performed in a few highly specialized institutions. However, with the latest advances in cryobiology, ovarian tissue cryopreservation is rapidly becoming a more widely offered technique by many medical centers around the world. The indications now extend beyond cancer. Even though the risk of re-implanting pre-existing cancer cells is minimal or non-existent for most types of cancer, this risk needs to be ascertained according to the cancer type and disease stage. The objective of this manuscript is to review the indications, risks and benefits of ovarian tissue cryopreservation.

Cancer treatment can cause changes in sex hormone production, premature ovarian failure and infertility. As survival rates for young cancer patients improve, protection against iatrogenic infertility caused by chemotherapy or radiotherapy assumes a higher priority.