First report on successful delivery after retransplantation of vitrified, rapid warmed ovarian tissue in Europe.

RESEARCH QUESTION: Cryopreservation of ovarian tissue is one feasible option to preserve female fertility prior to cancer treatment. The slow freezing protocol represents the current standard approach, while vitrification has been suggested as a promising alternative. This paper reports the follow-up and first successful delivery after retransplantation of vitrified, rapid warmed ovarian tissue in Europe. DESIGN: After the patient received a diagnosis of breast cancer, ovarian tissue was removed laparoscopically and sent via overnight transportation to University Hospital Bonn for vitrification on site. The patient was treated with chemotherapy, leading to ovarian failure. After 2 years, retransplantation of the vitrified, rapid warmed tissue was conducted on site. RESULTS: Two months after grafting, the patient reported regular menstrual cycles. After 1 further month a clinical pregnancy occurred, which ended in a spontaneous abortion at the 8th week of pregnancy. Six months after grafting, another naturally conceived pregnancy was determined, resulting in the birth of a healthy boy 14 months after retransplantation of the ovarian tissue. CONCLUSIONS: Complementing the successful deliveries reported by the groups of Suzuki (Japan) and Silber (USA) regarding vitrified tissue, the current results confirm the high potential of this cryopreservation method in a clinical routine setting as an alternative approach to the widespread slow freezing method.

Fertility protection: a novel approach using pretreatment with mesenchymal stem cell exosomes to prevent chemotherapy-induced ovarian damage in a mouse model.

BACKGROUND: Primary ovarian insufficiency refers to the loss of ovarian function before the age of 40 years and leads to amenorrhea and infertility. Primary ovarian insufficiency has diverse causes, but a common cause is exposure to gonadotoxic chemotherapy used in cancer treatment. Because of the risk for developing primary ovarian insufficiency, patients who want to preserve their fertility may consider various procedures for fertility preservation. However, current fertility preservation options are highly invasive, carry substantial risks, and have uncertain success rates. Recent studies from our group and others reported that mesenchymal stem cells and mesenchymal stem cell-derived exosomes can restore ovarian function in preclinical models of primary ovarian insufficiency by restoring damaged cells and inhibiting apoptosis. Although the restorative effect of mesenchymal stem cell-derived exosomes has been well reported in previous studies, the potential of mesenchymal stem cell-derived exosomes in preventing ovarian damage has not been fully elucidated. OBJECTIVE: This study hypothesized that the antiapoptotic potential of mesenchymal stem cell-derived exosomes may protect ovarian tissue from chemotherapy-induced damage. STUDY DESIGN: In this study, we delivered mesenchymal stem cell-derived exosomes directly into the ovaries of mice before administration of chemotherapy. A total of 60 mice were divided into 3 groups (20 per group), which were labeled the control, chemotherapy, and fertility protection groups. Only the fertility protection group mice received exosomes, whereas the control and chemotherapy group mice received saline. After exosome injection, the chemotherapy and fertility protection groups of mice were subjected to chemotherapy to induce ovarian damage. After chemotherapy, we evaluated the protective effects of exosome treatment on ovarian function, such as estrous cyclicity, serum hormone levels, and the fertility rate, by comparing these outcomes between the chemotherapy and fertility protection groups. These outcomes were also compared with those of the control group for comparison with outcomes under healthy conditions. RESULTS: After intraovarian injection of exosomes before chemotherapy, the mice were able to maintain their estrous cycle (4- to 5-day cyclicity), serum anti-müllerian hormone level (66.06±26.40 ng/mL, not significantly different from that of the healthy controls), folliculogenesis (32.2±11.3 in the chemotherapy group vs 46.4±14.1 in the fertility protection group; P<.05), expression of the steroidogenic acute regulatory protein gene (a the steroidogenesis marker) (0.44±0.11-fold expression in the chemotherapy group and 0.88±0.31-fold expression in the fertility protection group; P<.05), and fertility (2 of 8 in the chemotherapy group and 5 of 8 in the fertility protection group), thereby showing prevention of chemotherapy-induced damage. We found that exosome treatment before chemotherapy can preserve ovarian function and protect fertility through the overexpression of ATP synthase-binding cassette transporters, such as ABCB1b (10.17±17.75-fold expression in the chemotherapy group and 44.14±33.25-fold expression in the fertility protection group; P<.05) and ABCC10 (3.25±0.59-fold expression in the chemotherapy group and 5.36±1.86-fold expression in the fertility protection group; P<.05). CONCLUSION: In this study, we present a novel fertility protection method using mesenchymal stem cell-derived exosomes. We concluded that mesenchymal stem cell-derived exosomes are a promising and simple treatment option for fertility protection in reproductive-aged patients who are receiving gonadotoxic chemotherapy.

Cost-effectiveness analysis of ovarian function preservation with GnRH agonist during chemotherapy in premenopausal women with early breast cancer.

STUDY QUESTION: Is it economically worthwhile to use GnRH agonist (GnRHa) to prevent menopausal symptoms (MS) and protect fertility in premenopausal women with breast cancer (BC) during chemotherapy from the US perspective? SUMMARY ANSWER: It is cost-effective to administer GnRHa during chemotherapy in order to forefend MS in premenopausal patients with BC when the willingness-to-pay (WTP) threshold is $50 000.00 per quality-adjusted life-year (QALY), and to preserve fertility in young patients with BC who undergo oocyte cryopreservation (OC), or no OC, when the WTP thresholds per live birth are $71 333.33 and $61 920.00, respectively. WHAT IS KNOWN ALREADY: Chemotherapy often results in premature ovarian insufficiency (POI) in premenopausal survivors of BC, causing MS and infertility. Administering GnRHa during chemotherapy has been recommended for ovarian function preservation by international guidelines. STUDY DESIGN, SIZE, DURATION: Two decision-analytic models were developed, respectively, for preventing MS and protecting fertility over a 5-year period, which compared the cost-effectiveness of two strategies: adding GnRHa during chemotherapy (GnRHa plus Chemo) or chemotherapy alone (Chemo). PARTICIPANTS/MATERIALS, SETTING, METHODS: The participants were early premenopausal women with BC aged 18-49 years who were undergoing chemotherapy. Two decision tree models were constructed: one for MS prevention and one for fertility protection from the US perspective. All data were obtained from published literature and official websites. The models' primary outcomes included QALYs and incremental cost-effectiveness ratios (ICERs). The robustness of the models was tested by sensitivity analyses. MAIN RESULTS AND THE ROLE OF CHANCE: In the MS model, GnRHa plus Chemo resulted in an ICER of $17 900.85 per QALY compared with Chemo, which was greater than the WTP threshold of $50 000.00 per QALY; therefore, GnRHa plus Chemo was a cost-effective strategy for premenopausal women with BC in the USA. Probabilistic sensitivity analysis (PSA) results showed an 81.76% probability of cost-effectiveness in the strategy. In the fertility model, adding GnRHa for patients undergoing OC and those who were unable to undergo OC resulted in ICERs of $67 933.50 and $60 209.00 per live birth in the USA, respectively. PSA indicated that GnRHa plus Chemo was more likely to be cost-effective over Chemo when the WTP for an additional live birth exceed $71 333.33 in Context I (adding GnRHa to preserve fertility in young patients with BC after OC) and $61 920.00 in Context II (adding GnRHa to preserve fertility in young patients with BC who cannot accept OC). LIMITATIONS, REASONS FOR CAUTION: The indirect costs, such as disease-related mental impairment and non-medical costs (e.g. transportation cost) were not included. All data were derived from previously published literature and databases, which might yield some differences from the real world. In addition, the POI-induced MS with a lower prevalence and the specific strategy of chemotherapy were not considered in the MS model, and the 5-year time horizon for having a child might not be suitable for all patients in the fertility model. WIDER IMPLICATIONS OF THE FINDINGS: When considering the economic burden of cancer survivors, the results of this study provide an evidence-based reference for clinical decision-making, showing that it is worthwhile to employ GnRHa during chemotherapy to prevent MS and preserve fertility. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Natural Science Foundation of Fujian Province [2021J02038]; and the Startup Fund for Scientific Research, Fujian Medical University [2021QH1059]. All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

The effect of high-throughput vitrification of human ovarian cortex tissue on follicular viability: a promising alternative to conventional slow freezing?

BACKGROUND: The standard procedure most frequently used for ovarian tissue cryopreservation (OTC) is slow freezing, while vitrification has been proposed as promising alternative and has built an impressive catalog of success in fertility laboratories regarding cryopreservation of oocytes and embryos. METHODS: We developed and evaluated a high-throughput protocol for vitrification of human ovarian tissue suitable for clinical processing. Follicular viability was assessed via calcein staining prior and after cryopreservation analyzing ovarian tissue of a cohort of 30 patients. RESULTS: We found no significant differences regarding follicular viability between slow frozen and vitrified cortex tissue samples 24 h after thawing and rapid warming. Follicular viability of thawed and rapid warmed samples was not significantly different in comparison to fresh samples, indicating high proportions of follicular survival rates with both methods. CONCLUSIONS: High-throughput vitrification is a promising option in a clinical setting. More research is required to determine the status of other tissue-specific quality indicators potentially influencing on autotransplantation.

How much total ovarian tissue can be removed without compromising ovarian function? An animal study.

OBJECTIVE: Removal of ovarian tissue is a new option for fertility preservation for certain cancer patients in China. The aim was to investigate the impact of stepwise removed tissue on hormone levels and follicles in rats. METHODS: Six to ten-week old rats were divided into six groups (% total ovarian tissue): 1 = control (100%), 2 (75%), 3 (50%), 4 (25%), 5 (12.5%), 6 (0%, bilateral ovariectomy). Blood test was carried out fortnightly to assess estradiol (E2), progesterone (P), follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), and inhibin B (INHB). Ovaries are obtained from surgical resections and from rats sacrificed after 12 weeks. RESULTS: During 12 weeks, groups 4, 5, and 6 had higher FSH and lower AMH and INHB values compared to control (p< .05), but in group 4 E2 and P was not significantly different from control (p> .05). All ovarian function parameters stopped in groups 5 and 6. Follicle morphology was not significantly different between baseline and 12 weeks after surgery in groups 1-5. CONCLUSIONS: For the first time, we demonstrated that even up to 75% of total ovarian tissue can be removed without impact on E2 and P production in rats, which, if confirmed in women, would mean that hazardous (or possibly contraindicated in cancer patients) hormone therapy is not required to avoid the negative consequences of hormone depletion.

[Fertility preservation options before gonadotoxic antirheumatic treatment : A review]. / Fertilitätserhaltende Optionen vor gonadotoxischer antirheumatischer Therapie : Ein Überblick.

Cyclophosphamide is still clinically used in rheumatic diseases with severe disease courses. Cyclophosphamide has a pronounced gonadotoxic effect largely depending on the cumulative dose. The risk of amenorrhea is reported to be in the range of 12-54% and is dependent on the age of the patient at initiation of treatment. Every patient of reproductive age should therefore be offered counseling on options for fertility protection. There are 3 options for fertility protection: oocyte harvesting and cryopreservation after a hormonal stimulation of 10-14 days, ovarian wedge resection and cryopreservation and administration of a gonadotropin-releasing hormone (GnRH) agonist. The decision whether and, if so, which treatment should be performed is made in close consultation between the patient, rheumatologists and reproductive physicians and depends on the available treatment time window, the age of the patient and the severity of the underlying disease.

Identification of research priorities in infertility and assisted reproduction: an international, multicentre study.

RESEARCH QUESTION: What are the main research interests among patients of assisted reproductive technologies (ART)? DESIGN: Cross-sectional study consisting of an anonymous online survey sent to 2112 patients from eight centres in four countries in 2018. Patients were asked to identify research questions relevant to them in the field of infertility and ART. Answers were categorized into topics and ranked by frequency. A long list of the top 30 research topics was extracted from the aggregate results, from which a short list of the top 10 research topics was created. Ten research questions were finally formulated. RESULTS: A total of 945 responses were analysed. Main interests were side-effects, success rates, infertility prevention and emotional support. The 10 research questions were: 1. What are the side-effects of drugs used in ART treatments? (51.6%). 2. What are the most effective methods to cope with infertility from the psychological point of view? (35.7%). 3. What effects could diet have on fertility? (25.9%). 4. What are ART success rates per clinical profile? (24.8%). 5. Are there some habits and lifestyle factors that could prevent infertility? (20.0%). 6. What are the long-term risks associated with ART in mother and child? (18.5%). 7. Are alternative therapies such as acupuncture, yoga and meditation effective to treat/prevent infertility? (18.5%). 8. What is the impact of exercise on fertility? (15.4%). 9. How does oocyte quantity and quality affect fertility? (9.5%). 10. What are the genetic patterns or hereditary conditions causing/related to infertility? (9.5%). CONCLUSIONS: Researchers and clinicians should keep in mind that, in addition to success rates and safety, patients greatly value research into causes, prevention and emotional aspects of infertility.

Determinants of utilization of cryopreservation of germ cells in adolescent cancer patients in four European countries.

Infertility is a relevant late-effect following cancer treatment; yet, a large proportion of survivors cannot recall having been informed of this risk. In an intervention study, we examined if and how supportive patient information material on fertility/fertility-preserving measures influences utilization of cryopreservation in adolescent cancer patients. The control group, recruited 03/2014-01/2016, received the usual patient education at initial diagnosis. The intervention group, recruited 04/2016-10/2017, received patient education supported by a fertility flyer and brochure. Patients and parents were each asked questions on utilization of cryopreservation in a questionnaire 3 and 6 months after initial diagnosis. Patient core and therapy data were obtained from medical records. Overall, cryopreservation rates showed no significant difference between the control (32.7%, n = 37/113) and intervention group (36.6%, n = 37/101). In the control group, cryopreservation was associated with gender (OR 0.100, CI 0.023-0.427), age (OR 1.559, CI 1.077-2.258) and recalling information on fertility protection (OR 33.663, CI 2.100-539.574); in the intervention group, cryopreservation was related to gender (OR 0.093, CI 0.026-0.330) and the estimated infertility risk (OR 43.665, CI 2.157-883.974).Conclusion: Cryopreservation rates did not overall increase following the intervention; however, the individual risk seemed to be brought into attention more: Those at risk, including younger patients, cryopreserved at higher rates.What is Known:•Infertility is a relevant late-effect following adolescent cancer.•Guidelines recommend to offer fertility protection before cancer treatment.•A relevant proportion of adolescents with cancer are not aware of this risk.•Fertility protection seems under-used in cancer patients at risk for infertility.What is New:•Information material on fertility and protection in adolescents did not increase overall rates of cryopreservation.•Cryopreservation rates were improved according to individual risk for infertility.•Our flyers and brochures on fertility in cancer patients are available in various languages.

[An investigation of the fertility needs of young patients with breast cancer].

Objective: To investigate the fertility needs and outcome of pregnancy in patients with young breast cancer in China. Methods: A retrospective cross-sectional investigation was conducted on 374 young breast cancer women from Cancer Hospital, Chinese Academy of Medical Sciences. Young patients with breast cancer were defined as patients who got initial diagnosis of breast cancer at age no more than 40 years old. We conducted a questionnaire survey and collected clinical data from medical chart. Logistic regression model was used to analyze the possible factors influencing patients' fertility intention. Results: 308 young women with breast cancer completed questionnaires, and the response rate was 82.4%. 81 patients (26.3%) had fertility needs after diagnosis. Of them, 6 cases took active measures to preserve fertility. 72 patients (23.4%) received fertility counseling during treatment. 7 patients were successfully pregnant, including four cases who delivered normally. Multivariate logistic regression analysis showed that patients under 35 years old (OR=4.81), bachelor degree or above (OR=3.26), receiving breast-conserving surgery (OR=2.15) and childless patients (OR=3.03) were more likely to have fertility needs after diagnosis of breast cancer (all P<0.05). Conclusions: The fertility needs of young breast cancer women in China are gradually increasing. Healthcare providers associated with tumor patients should actively offer corresponding fertility consultation and individualized diagnosis and therapy plans for patients with fertility needs.

Ovarian tissue cryopreservation: prospective randomized study on thawed ovarian tissue viability to estimate the maximum possible delivery time of tissue samples.

Ovarian tissue cryopreservation is one of the most important methods to protect female fertility, but we just recently established the first central laboratory in China, now building a network with other hospitals. The aim was to estimate the thawed ovarian tissue viability and to explore the feasibility of short-distance transportation. Fifteen samples were obtained from each of 11 patients, i.e. in total 165 samples. One fresh sample was used for follicle counts, 14 punches were cryopreserved, thawed, and randomly divided into seven groups depending on the time after thawing: 0, 20, 40, 60, 80, 100, 120 min. Follicle counts, steroid hormones, and lactate levels were assessed. No significant differences for the three parameters of tissue viability comparing the seven groups were seen. The time can last up to two hours for the delivery of tissue samples from the laboratory to the surgery room. To our knowledge, this question has been tested for the first time systematically within a prospective randomized comparative study.

Are women and men well informed about fertility? Childbearing intentions, fertility knowledge and information-gathering sources in Portugal.

BACKGROUND: The postponement of parenthood may increase the number of couples experiencing infertility and prolonged time to pregnancy. Previous research has revealed that childless people are not well informed regarding fertility, which may threat their childbearing intentions. This study aimed to examine fertility knowledge and childbearing intentions held by Portuguese people and their use and perceived usefulness of information sources on fertility. METHODS: Participants were recruited using a random-route domiciliary approach. A total of 2404 individuals aged 18-45 were asked to complete a structured questionnaire evaluating socio-demographic characteristics, childbearing intentions, fertility knowledge and information-gathering sources regarding fertility. RESULTS: In total, 95.5% of the participants indicated the desire to have children in the future, and 61.7% reported that having children would contribute to life satisfaction. Most of the participants expressed the desire to have two children in the future. The discrepancy between the numbers of planned and desired children was higher in men, in participants with lower education levels, in professionally active participants and in the unemployed participants. Relationship stability seemed to be more important in influencing childbearing decisions than financial stability or family support. Participants' knowledge regarding fertility was poor. Women, the participants who were older than 25, the participants with longer education and the participants with higher income exhibited the greatest levels of knowledge of fertility, although this knowledge was only slightly enhanced in these subgroups. Also, the participants overestimated both the chances of spontaneous pregnancy and the success rates of assisted reproduction techniques. Finally, the results revealed that websites were the main information sources used by the participants and only 18.0% of the participants had previously discussed fertility issues with their doctors. CONCLUSIONS: Although Portuguese men and women reported the desire to have children in the future, their knowledge regarding fertility and infertility risk was poor. In addition, participants used more general sources of information, such as website, but not specialized sources, such as their doctors. There is a real need to work with general practitioners to empower them to provide adequate fertility information to every childless patient.

Expert consensus on diagnosis, treatment and fertility management of young breast cancer patients.

Breast cancer in young females is a relatively common disease in China. Young breast cancer has aggressive clinical and pathological features. During the treatment of young females with breast cancer, issues involving the choice of surgical methods, early amenorrhea, and fertility protection may have physical, psychological, and social impacts. Thus, a multidisciplinary model of diagnosis and treatment is indispensable. The breast cancer expert committee of the National Cancer Quality Control Center organized experts in related fields in China to compile this consensus as to provide scientific and feasible solutions for rational diagnosis, treatment, and fertility management for young females with breast cancer. This consensus is based on the literature data, the views of relevant international guidelines, and the clinical practice experience of experts in different fields.

Concept Paper on the Technique of Cryopreservation, Removal and Transplantation of Ovarian Tissue for Fertility Preservation.

The cryopreservation of ovarian tissue with subsequent transplantation of the tissue represents an established method of fertility protection for female patients who have to undergo gonadotoxic therapy. The procedure can be performed at any point in the cycle and thus generally does not lead to any delay in oncological therapy. With the aid of this procedure, more than 130 births to date worldwide have been able to be recorded. The birth rate is currently approximately 30% and it can be assumed that this will increase through the further optimisation of the cryopreservation and surgical technique. The concept paper presented here is intended to provide guidance for managing cryopreservation and transplantation of ovarian tissue to German-speaking reproductive medicine centres.

[Solutions against Declining Birthrates Confronting Japan's Aging Society by Supporting Female Workers in Harmonizing Work with Their Health and Social Issues: Fertility, Chronic Illness, and Raising Children].

Japan is currently facing serious social problems related to low birth rates and aging. We propose two possible solutions from the perspective of occupational health. First, companies should establish support systems to help working women with pregnancy and childbirth. Such systems would require the cooperation and understanding of coworkers, including men, and the introduction of flexible work schedules that are also designed to allow workers to care for family members with disabilities. Additionally, with regard to the protection and promotion of the fertility of working women, occupational health staff members should provide education to working women regarding appropriate lifestyle choices in areas such as diet, prevention of work-related health problems, and mental health before and after childbirth. Moreover, workers undergoing assisted reproductive technology procedures should be supported as they experience physical, mental, and economic burdens associated with this process. Second, companies should guarantee the right of workers to take a sick leave and then return to work so they can balance work and the need to treat chronic conditions. Occupational staff members should follow up employees who return to work, by offering, for example, mental health care to cancer survivors. They should also play important roles in preventing the exacerbation of disease and empowering workers to continue their visits to medical institutions. Collaborative study bridges between companies and medical institutions are necessary for the promotion of these harmonization schemes.

Chapter 15 Development of a Nationwide Network for Ovarian Tissue Cryopreservation.

Ovarian tissue cryopreservation is gaining much interest since the publication of the first live birth after retransplantation of frozen-thawed tissue in 2004 (Donnez et al., Lancet 364:1405-1410, 2004). In contrast to cryopreservation of gametes and embryos, ovarian tissue freezing is a complex requiring a proper approach in order to make this a viable option for fertility preservation of cancer patients. Due to the need in terms of laboratory space, equipment, personnel, and adequate logistics, an ovarian tissue cryobank is most economic if managed as a centralized service unit that interacts with numerous clinics covering the surgical part. Transportation of ovarian tissue under appropriate conditions from the surgical unit to the cryobank for subsequent preparation and freezing has been shown to have no impact on cryo-survival (Schmidt et al., Hum Reprod 18:2654-2659, 2003; Isachenko et al., Fertil Steril 91:1556-1559, 2009). Several children have been born after retransplantation of such tissue that was derived from the cryobank in Bonn, Germany (Homepage FertiPROTEKT. http://www.fertiprotekt.de ). This cryobank is one of the largest in the world with more than 1300 tissue samples that were frozen from 2003 until today. It is integrated in the network FertiPROTEKT (Homepage FertiPROTEKT. http://www.fertiprotekt.de ) and is served by 108 surgical centers that are located all over Germany. The concept of this cryobank is a blueprint for success and has recently been used for another regionally centralized cryobank in Beijing, China. In this chapter the most important topics that need to be considered while creating a centralized cryobank within a national or regional network are highlighted.

Mechanisms of chemotherapy-induced ovarian damage in breast cancer patients.

Fertility preservation in breast cancer patients is an increasingly relevant topic. In the present paper we review available data on the mechanism of ovarian damage caused by anticancer agents currently used for the treatment of breast cancer. We also describe current methods to preserve fertility including oocytes or ovarian tissue freezing and administration of LH-RHa during chemotherapy. The aim of the paper is to provide clinical oncologists with an adequate knowledge of the subject to enable them to give a correct counselling to young women that must receive chemotherapy and want to increase their possibilities of maintaining fertility.

Surgical Aspects of Ovarian Tissue Removal and Ovarian Tissue Transplantation for Fertility Preservation.

Introduction: The removal of ovarian tissue prior to starting oncologic treatment and the subsequent transplantation of this tissue after completing therapy have become increasingly important surgical fertility-preserving techniques. The aim of this review was to investigate the different surgical techniques used for this method reported in the literature to date and to discuss the advantages and disadvantages of the respective techniques. Review: A search was done in MEDLINE using a defined algorithm to find studies published between January 2004 and December 2015. All study designs were included in our review if they contained statements on the surgical technique used. We found 16 publications (8 retrospective cohort studies, 6 case reports and 2 systematic reviews) with a total of 1898 female patients which reported on the surgical technique used for ovarian biopsy and 15 publications (7 retrospective cohort studies, 6 case reports and 2 systematic reviews) with a total of 455 women which mentioned the surgical technique used for ovarian transplantation. Different surgical techniques can be used both for ovarian biopsy and for the transplantation of ovarian tissue. A number of different surgical routes have been used, and the amount of tissue extracted, the instruments used, the treatment of the ovary, the transplantation site, the blood supply to the transplanted ovarian tissue and the procedure used for simultaneous surgical interventions vary. Conclusion: In future, one of the tasks will be to establish a standard surgical method for ovarian extraction and transplantation which will have a low rate of complications and a high pregnancy and birth rate while ensuring that the transplanted tissue is fully functional.

First retransplantation of cryopreserved ovarian tissue following cancer therapy in Germany.

INTRODUCTION: New anticancer treatments have increased survival rates for cancer patients but often at the cost of sterility. One way of preserving fertility in these patients is the use of cryopreservation of ovarian tissue with subsequent retransplantation following a period of recurrence-free survival. We report the follow-up of the first case of retransplantation of ovarian tissue in Germany. METHODS: Immediately following the diagnosis of anal cancer, ovarian tissue was removed laparoscopically, and cryopreserved. The patient was then treated with combined radiochemotherapy, which resulted in iatrogenic premature ovarian failure, and was associated with inhibin B serum levels lower than 10 ng/L. After the 2.5 year period of cancer remission, the cryopreserved ovarian tissue was retransplanted orthotopically. RESULTS: Five months later estradiol serum levels had risen from lower than 20 pg/mL to 436 pg/mL. Three ovarian follicles were detected ultrasonographically in the pelvic side wall. Finally the patient reported her first menstruation after the intervention. The endocrine activity of the transplanted cryopreserved tissue has demonstrated viability, and the ability to develop. DISCUSSION: Cycle monitoring and timed intercourse should now help to achieve conception. These first results from Germany for retransplantation of cryopreserved ovarian tissue clearly show its potential for preserving fertility.