Options for preserving fertility in women undergoing gonadotoxic treatment
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Cancer chemotherapy and radiotherapy can be toxic to the ovaries, but women can improve their chances of preserving their fertility. Three options are available: gonadotropin-releasing hormone (GnRH) analogues, oocyte cryopreservation, and ovarian tissue cryopreservation. A fourth option, ovarian transposition, is valid for patients undergoing pelvic radiation but is not useful in patients undergoing chemotherapy.Keywords:
Oocyte cryopreservation
Ovarian Tissue Cryopreservation
Premature ovarian failure
Gonadotropin
Fertility Preservation is an essential part of cancer care when treating young females and men. While semen cryopreservation is a straightforward approach for postpubertal men and there is the option of experimental testicular tissue freezing for prepubertal boys, the options for females are more tumultuous. The last 17 years brought us established approaches such the embryo and oocyte cryopreservation and the ovarian cryopreservation is ready to join the list. However, there still is no proven medical fertility preservation method and the controversy around the utility of GnRHa continues.
Oocyte cryopreservation
Ovarian Tissue Cryopreservation
Embryo cryopreservation
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Ovarian Tissue Cryopreservation
Oocyte cryopreservation
Premature ovarian failure
Embryo cryopreservation
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Summary Several options are currently available for the preservation of fertility in cancer patients: embryo cryopreservation, oocyte cryopreservation or ovarian tissue cryopreservation. The choice of the most suitable strategy for preserving fertility depends on different parameters: the type and timing of chemotherapy, the type of cancer, the patient’s age and the partner status. Cryopreservation of ovarian tissue is the only option available for prepubertal girls and woman who cannot delay the start of chemotherapy. So far, 15 live births have been obtained after orthotopic transplantation of cryopreserved ovarian tissue.
Ovarian Tissue Cryopreservation
Oocyte cryopreservation
Embryo cryopreservation
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Most female cancer patients of reproductive age do not have the option of utilising in vitro fertilisation (IVF) and embryo cryopreservation to safeguard their fertility. Indeed, in many cancers chemotherapy is initiated soon after diagnosis. For patients who require immediate chemotherapy, or those with hormone-sensitive cancer or who are still pre-pubertal, the practice of oocyte and ovarian tissue cryopreservation has rapidly become the technique of choice, although it remains experimental. Cryopreservation of oocytes can be performed in single women who are able to undergo a stimulation cycle, but the effectiveness of this technique is still low, with delivery rates of 1–5% per frozen–thawed oocyte. Nevertheless, since the recent introduction of oocyte vitrification, the delivery rates are about two-fold per thawed oocyte. Cryopreservation of ovarian tissue is the only option available for pre-pubertal girls and for woman who cannot delay the start of chemotherapy. Ovarian cryopreservation and transplantation procedures have so far yielded six live births in humans after autologous transplantation.
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Ovarian Tissue Cryopreservation
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The study describes clinical management and outcomes of currently available fertility preservation techniques in a set of 154 young female cancer patients.Patients in reproductive age with newly diagnosed cancer were offered embryo or oocyte cryopreservation, ovarian tissue cryopreservation and the administration of GnRH analogues during chemotherapy. Particular attention was given to the technical aspects and clinical application of these fertility preservation techniques.During the study period (2004-2009), 154 young female cancer patients were offered fertility preservation counseling. Patient's average age was 29.4 years and average parity was 0.7 children. Administration of GnRH analogues (n = 123, 79.9%) and ovarian tissue cryopreservation (n = 15, 9.7%) were the most commonly used fertility preservation strategies. In 20 cases (16.1%), the combination of several fertility preservation techniques was offered to individually selected patients.Combination of fertility preservation techniques gives young cancer patients the best chance for future fertility and should be concentrated in specialized centers.
Oocyte cryopreservation
Ovarian Tissue Cryopreservation
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The aim of this study is to report the current status of ovarian tissue cryopreservation among alternatives for fertility preservation in the Nordic countries.A questionnaire was sent to 14 Nordic academic reproductive centers with established fertility preservation programs. It covered fertility preservation cases performed up to December 2014, standard procedures for ovarian tissue cryopreservation and oocyte cryopreservation and reproductive outcomes following ovarian tissue transplantation.Among the Nordic countries, Denmark and Norway practice ovarian tissue cryopreservation as a clinical treatment (822 and 164 cases, respectively) and their programs are centralized. In Sweden (457 cases), ovarian tissue cryopreservation is practiced at five of six centers and in Finland at all five centers (145 cases). Nearly all considered ovarian tissue cryopreservation to be experimental. In Iceland, embryo cryopreservation is the only option for fertility preservation. Most centers use slow-freezing methods for ovarian tissue cryopreservation. Most patients selected for ovarian tissue cryopreservation were newly diagnosed with cancer and the tissue was predominantly retrieved laparoscopically by unilateral oophorectomy. Only minor complications were reported. In total, 46 women have undergone ovarian tissue transplantation aiming at recovering fertility, 17 healthy children have been born and several additional pregnancies are currently ongoing. Whenever patients' clinical condition is permissive, oocyte cryopreservation after hormonal stimulation is preferred for fertility preservation. Between 2012 and 2014, a smaller proportion of females have undergone fertility preservation in the Nordic centers, in comparison to males (1:3).Overall, ovarian tissue cryopreservation was reported to be safe. Slow freezing methods are still preferred. Promising results of recovery of fertility have been reported in Nordic countries that have initiated ovarian tissue transplantation procedures.
Ovarian Tissue Cryopreservation
West germany
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The preservation of fertility is an integral part of care of children requiring gonadotoxic treatments for cancer or non-malignant diseases. In France, the cryopreservation of ovarian tissue has been considered and has been offered as a clinical treatment since its inception. The aim of this study is to review 20 years of activity in fertility preservation by ovarian tissue cryopreservation (OTC) for children and the feasibility of oocyte isolation and cryopreservation from the ovarian tissue at a single center. Retrospective study including patients aged 15 years or younger who underwent OTC, combined for some with oocyte cryopreservation of isolated oocytes, before a highly gonadotoxic treatment for malignant or non-malignant disease was initiated. We describe the evolution of activities in our program for fertility preservation and patient characteristics at the time of OTC and follow up. From April 1998 to December 2018, 418 girls and adolescents younger than 15 years of age underwent OTC, representing 40.5% of all females who have had ovarian tissue cryopreserved at our center. In all, 313 patients had malignant diseases and 105 had benign conditions. Between November 2009 and July 2013, oocytes were isolated and also cryopreserved in 50 cases. The mean age of patients was 6.9 years (range 0.3-15). The most frequent diagnoses in this cohort included neuroblastoma, acute leukemia and hemoglobinopathies; neuroblastoma being the most common diagnosis in very young patients. During follow up, three patients requested the use of their cryopreserved ovarian tissue. All had undergone ovarian tissue transplantation, one for puberty induction and the two others for restoring fertility. So far, no pregnancies have been achieved. Eighty-four patients who had OTC died. Ovarian tissue cryopreservation is the only available technique for preserving fertility of girls. To our knowledge this is the largest series of girls and adolescents younger than 15 years so far reported on procedures of OTC before highly gonadotoxic treatment in a single center.
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Oocyte cryopreservation
Ovarian Tissue Cryopreservation
Embryo cryopreservation
Live birth
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The preservation of fertility in female cancer survivors has become an important health issue. The different cryopreservation options available for fertility preservation are embryo, oocyte, and ovarian tissue cryopreservation. Oocyte cryopreservation is available for women without partners, but there is a limited experience with this technique and the pregnancy rate is still low. In spite of recent reports of successful birth after autotransplantation of cryopreserved-thawed human ovarian cortical tissues, clinical experience is also limited and this technique remains still experimental. Whole ovary cryopreservation itself poses several challenges. Further researches for establishing optimal cryopreservation and thawing protocols and increasing post-thawing survival, pregnancy, and delivery rates are necessary. In this article, the strategies for fertility preservation in cancer survivors are discussed. The different options and their results are discussed, as well as their indications, efficacy and ethical issues.
Oocyte cryopreservation
Ovarian Tissue Cryopreservation
Autotransplantation
Embryo cryopreservation
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Oocyte cryopreservation
Ovarian Tissue Cryopreservation
Embryo cryopreservation
Ovarian Reserve
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