Murat Sönmezer

Cryopreservation and autotransplantation of human ovarian tissue prior to cytotoxic therapy--a technique in its infancy but already successful in fertility preservation.

Increasing survival rates in young cancer patients, new reproductive techniques and the growing interest in quality of life after gonadotoxic cancer therapies have placed fertility preservation as an important issue to oncologists, fertility specialists and patients. Several techniques are now available for fertility preservation in these patients. A new promising method is cryopreservation and transplantation of ovarian cortex. Ovarian tissue can be extracted by laparoscopy without any significant delay of gonadotoxic therapy. The tissue can be cryopreserved by specialised centres of reproductive medicine and transplanted in case the women experience premature ovarian failure (POF). This review summarises the European expertise on cryopreservation and transplantation of ovarian tissue, following around 30 reported transplantations globally, resulting in six live births and several ongoing pregnancies. It emphasises that fertility preservation by the cryopreservation of ovarian tissue is a new but already a successful clinical option, which can be considered for selected cancer patients.

Random-start controlled ovarian hyperstimulation for emergency fertility preservation in letrozole cycles.

OBJECTIVE To report an emergency approach of random-start controlled ovarian hyperstimulation (COH) in the late follicular or luteal phase of the menstrual cycle for embryo cryopreservation in patients with cancer. DESIGN Case series. SETTING Academic tertiary referral centers. PATIENT(S) Three patients with a diagnosis of breast cancer requiring emergency fertility preservation in the late follicular or luteal phase of the menstrual cycle. INTERVENTION(S) After baseline pelvic ultrasound and hormonal evaluation, random-start COH was commenced immediately on menstrual cycle days 11, 14, or 17 with use of letrozole 2.5 mg/d and recombinant FSH 150 to 300 IU/d. Gonadotropin-releasing hormone antagonist was administered to prevent ovulation in all cases. Ovulation was triggered with either 250 μg of recombinant hCG or 10,000 IU of urinary hCG. MAIN OUTCOME MEASURE(S) Number of oocytes harvested, maturity and fertilization rates, number of embryos frozen. RESULT(S) Nine to 17 oocytes were harvested, resulting in the freezing of seven to 10 embryos with the mean maturity and fertilization rates of 58.8% to 77.7% and 69.2% to 87.5%, respectively. CONCLUSION(S) In an emergent setting, ovarian stimulation can be started at a random cycle date for the purpose of fertility preservation without compromising fertilization rates in letrozole cycles.

Ovarian tissue cryopreservation: benefits and risks.

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 reimplanting 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.

Chemotherapy and amenorrhea: risks and treatment options.

Purpose of review The purpose of this study is to review the impact of chemotherapy on fertility and to update the reader on the current state of fertility preservation techniques. Recent findings Chemotherapy results in irreversible damage to ovarian follicles and stromal function, and alkylating agents cause the most significant damage to ovarian reserve. Options for fertility preservation range from well established techniques such as embryo cryopreservation to experimental ones such as ovarian tissue freezing. The safety and effectiveness of concomitant use of gonadotropin-releasing hormone analogues to prevent chemotherapy-induced follicle death is still debated. In-vitro maturation of germinal vesicle oocytes can be an option in patients who do not have sufficient time for ovarian stimulation. Summary The impact of chemotherapy on future fertility is much more significant than is widely believed. Because of this, young females should be counseled about fertility preservation options. Fertility preservation requires an individualized approach. If possible these patients should be encouraged to utilize the most established assisted reproductive techniques. Although success of IVF with frozen-thawed embryos now approaches that of using fresh embryos, success rates with oocyte freezing are lower but these rates are on the rise. Even though ovarian tissue cryopreservation is still an experimental technique, currently it is the only fertility preservation option in children.

Microdose gonadotropin-releasing hormone agonist flare-up protocol versus multiple dose gonadotropin-releasing hormone antagonist protocol in poor responders undergoing intracytoplasmic sperm injection–embryo transfer cycle

OBJECTIVE To compare the efficacy of microdose GnRH agonist (GnRH-a) flare-up and multiple dose GnRH antagonist protocols in patients who have a poor response to a long luteal GnRH-a protocol. DESIGN Prospective, randomized, clinical study. SETTING University hospital. PATIENT(S) Forty-two poor responder patients undergoing intracytoplasmic sperm injection (ICSI)-embryo transfer cycle. INTERVENTION(S) Twenty-one patients received microdose leuprolide acetate (LA) (50 microg twice daily) starting on the second day of withdrawal bleeding. The other 21 patients received 0.25 mg of cetrorelix daily when the leading follicle reached 14 mm in diameter. MAIN OUTCOME MEASURE(S) Serum E(2) levels, number of growing follicles and mature oocytes, embryo quality, dose of gonadotropin used, cancellation, fertilization, implantation rate and pregnancy rate (PR). RESULT(S) The mean serum E(2) concentration on the day of hCG administration was significantly higher in the microdose GnRH-a group than in the GnRH antagonist group (1,904 vs. 1,362 pg/mL). The clinical PRs per started cycle of microdose GnRH-a and GnRH antagonist groups were 14.2% and 9.5%, respectively. There were no statistically significant differences in the other ovulation induction characteristics, fertilization and implantation rates. CONCLUSION(S) Microdose GnRH-a flare-up protocol and multiple dose GnRH antagonist protocol seem to have similar efficacy in improving treatment outcomes of poor responder patients.

Orthotopic and heterotopic ovarian tissue transplantation.

Although still experimental, cryopreservation and transplantation techniques for ovarian tissue have been well described, and a number of successful human pregnancies have occurred. Ovarian cryopreservation is the only fertility preservation procedure that can be offered to prepubertal children, and when cytotoxic treatment is urgent. There are two main approaches for autotransplantation of human ovarian tissue. In the heterotopic transplantation, cortical fragments can be grafted subcutaneously at various sites whereas in orthotopic transplantation cortical pieces are transplanted into its original location. Both approaches have their own advantages and disadvantages. While natural pregnancy can occur in orthotopic transplantation, heterotopic transplantation may be indicated if the pelvis is not suitable for transplantation due to previous radiation or severe scar formation. Furthermore, tissue monitoring may be easier in the heterotopic site. In this article, we reviewed the indications, limitations, risks and transplantation techniques for ovarian tissue.

Myomectomy during cesarean section

The aim of this study is to evaluate the intra and post-operative risks of myomectomies during cesarean section. It was reported that it would be better to avoid myomectomies at cesarean section unless the myoma are pedunculated and can easily be excised considering the risk of uncontrolw x lable hemorrhage 1 . In this study, we report our experience of 22 myomectomies performed for Ž . large myomas )5 cm during cesarean section, between May 1994 and September 1998 at the Department of Gynecology in Ankara University Hospital. Indications for myomectomies include: Ž patients’ desire, symptomatic pain, labor obstruc. tion malpresentation myomas, probability of adverse effect for future pregnancies, and post-operative complications. Our technique comprises performing a linear uterine incision as well as possible on the most prominent part of the leiomyoma avoiding sec-

Hormone replacement therapy, C-reactive protein, and fibrinogen in healthy postmenopausal women

OBJECTIVE To investigate short-term and long-term effects of combined hormone replacement therapy (HRT) on C-reactive protein (CRP) and fibrinogen plasma concentrations in healthy postmenopausal women. METHODS In this cross-sectional study 241 healthy postmenopausal women were enrolled. A total of 81 women were receiving the following treatments for 3 months; transdermal 17beta-estradiol (17beta-E2) + medroxyprogesterone acetate (MPA) (n = 21), oral 17beta-E2 + norethisterone acetate (NETA) (n = 27), and conjugated equine estrogens (CEE) + MPA (n = 33). The same combined therapies were implemented in another 58 women for 12 months; transdermal 17beta-E2 + MPA (n = 10), oral 17beta-E2 + NETA (n = 16), and CEE + MPA (n = 32). Control group included 102 healthy postmenopausal women not receiving HRT. The effect of the type and the duration of HRT regimens on plasma levels of CRP, fibrinogen and lipids were investigated. RESULTS Median CRP concentrations were significantly higher in women receiving oral 17beta-E2 + NETA (P = 0.037) and CEE + MPA (P = 0.0001) for 3 months than in women taking the same types of HRT for 12 months and of those were not on HRT. Median CRP levels were similar in women taking transdermal 17beta-E2 + MPA for 3 and 12 months, compared with controls. Fibrinogen levels were not different between nonusers and any group of HRT users. CONCLUSIONS These elevated levels of CRP, which appears very recently as a crucial marker for cardiovascular disease, may be responsible for the early increased cardiovascular risk after starting oral combined HRT. But this increased risk in the early period seems to decrease with long-term use. Transdermal 17beta-E2 + MPA had insignificant effect on CRP both in short-term or in long-term use.

The role of low-molecular-weight heparin in recurrent implantation failure: a prospective, quasi-randomized, controlled study.

Low-molecular-weight heparin did not provide any beneficial effect on pregnancy outcomes in patients with two or more implantation failures. Further trials are needed to confirm a trend in favor of low-molecular-weight heparin in the subgroup with women with three or more implantation failures.

Assisted reproduction and fertility preservation techniques in cancer patients.

Purpose of reviewThis study aims to review the current state of different fertility preservation options in patients facing the risk of gonadal failure. Recent findingsVarious malignant and nonmalignant diseases have been successfully treated with high-dose chemotherapy or radiotherapy. Even though many young patients receiving these treatments are at risk of developing reproductive failure, a number of fertility preservation options ranging from embryo cryopreservation to ovarian tissue cryopreservation are now available. SummaryEmbryo cryopreservation is a well established technique to preserve fertility. The success rate with oocyte cryopreservation has been on the rise. Both oocyte and embryo freezing require ovarian stimulation and novel ovarian stimulation regimens utilizing aromatase inhibitors which have been developed for ovarian stimulation in women with estrogen sensitive cancer. Even though ovarian tissue cryopreservation is a novel technology, it is the only fertility preservation option for children and the only treatment strategy that can restore ovarian function. In-vitro maturation is a promising technology and can be applied in combination with ovarian tissue cryopreservation.