Purpose
Aim of this prospective observational study was to analyze fertility status of Hodgkin lymphoma (HL) patients treated with different types of chemotherapy while receiving GnRH analogues to ...preserve ovarian function.
Methods
Fertility status was assessed among 108 females in reproductive age treated by curative chemotherapy for freshly diagnosed HL between 2005 and 2010 in university-based tertiary fertility and oncology center. All patients received GnRH analogues during chemotherapy to preserve their ovarian function. Their reproductive functions were assessed by follicle-stimulating hormone (FSH) measurement and pregnancy achievement. Ovarian function was determined separately in three groups with increasing gonadotoxicity of chemotherapy.
Results
One year following the treatment, normal ovarian function was found in 89 (82.4 %) of patients. Two years after chemotherapy, 98 (90.7 %) of patients retained their ovarian function, and 23 (21.3 %) achieved clinical pregnancy during the follow-up period. Average FSH after chemotherapy was 11.6 ± 17.9 IU/l 1 year after the treatment resp. 9.0 ± 13.8 at the 2 years interval. There were significantly more patients with chemotherapy induced diminished ovarian reserve (chDOR) among the group receiving escalated BEACOPP chemotherapy in comparison with the other types of treatment (58.1 % vs. 87.9 % resp. 95.5 %).
Conclusion
The rate of chDOR is significantly higher after EB poly-chemotherapy and there is no tendency for improvement in time. The 2 + 2 chemotherapy with GnRH-a required for more advanced HL retained ovarian function significantly better after 2 years. Another important advantage of GnRH-a co-treatment is the excellent control of patient’s menstrual cycle.
BACKGROUND Frequent negative consequence of chemotherapy (CHT) is ovarian damage and premature ovarian failure (POF). Aim of this prospective case–control study is evaluation of GnRH analogue ...(GnRH-a) administration to patients with Hodgkin lymphoma (HL) during CHT and prevention of ovarian damage depending upon CHT regimen. METHODS Study group consists of 72 patients in fertile age (18–35 years) with HL diagnosis treated in 2004–2005 by curative CHT together with GnRH analogue (Triptorelin) administration according to a standardized protocol. Patients were divided into three groups according to the stage of disease and treated by three types of CHT regimens (A,B,C) with increased cytotoxicity. Ovarian function of all patients was assessed by gonadotrophin levels (FSH, LH) analysis from peripheral blood before treatment and also 6 and 12 month after it. The number of women with POF after CHT in study group was compared with control group (n = 45, age 18–35 years) of patients treated in 2002–2003 according to the same protocol but without protective GnRH analogue application. RESULTS In study group with GnRH analogue administration during CHT, there was significantly (P < 0.001) fewer cases with POF 6 and 12 month after the end of CHT (37.5% and 20.8%, respectively) than in control group (73.3% and 71.1%, respectively). Comparative analysis depending on cytotoxicity of CHT regimen used showed significant differences in percentage of patient with acquired POF between study and control group only in less aggressive CHT protocols. CONCLUSIONS Study showed a significant reduction of ovarian failure risk in women with HL treated with less aggressive CHT regimens plus a GnRH analogue.
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.
High-dose chemotherapy followed by autologous stem cell transplantation can improve the outcome of relapsed and refractory Hodgkin's disease (HD) patients. The objective of the trial was to determine ...the mobilizing potential of the DHAP salvage regimen (dexamethasone, cytarabine, cisplatin) for the collection of peripheral blood stem cells (PBSC) in patients with relapsed HD. The target yield of harvesting CD34 + cells was > or =2 x 10(6)/kg in order to support the subsequent myeloablative chemotherapy. Most of the 105 patients included were intensively pre-treated with different combination chemotherapy regimens prior to mobilization. The use of DHAP followed by granulocyte colony-stimulating factor (G-CSF; 10 microg/kg) resulted in the successful collection of adequate numbers of PBSC in 97.1% of patients (102 of 105) with a median harvest of CD34+ cells of 13 x 10(6)/kg (range 2.6 - 85.1). More than 2.0 x 10(6) CD34+ cells/kg were achieved in 65 of 103 (63%) patients after 1 apheresis, the maximum number of aphereses for all patients was 3. It was found that the optimal time of PBSC harvest was at days 13 - 16 after initiating the mobilization regimen. These results demonstrate that the salvage chemotherapy regimen, such as DHAP combined with G-CSF, can be successfully used to mobilize PBSC in HD patients.
Malignant disease and the therapy are major factors that may result in complete loss of fertility. There are several strategies for fertility preservation in fertile women faced with cancer. A modern ...and potentially effective method of reproductive function protection is ovarian tissue cryopreservation.
This paper summarizes the medical and scientific knowledge in this interesting multidisciplinary medical field. Furthermore, the authors' own experience with this novel and interesting method of ovarian tissue protection is presented. Ovarian tissue was obtained during laparoscopic surgery in five nuliparous women (aged 19-33) with a diagnosis of lymphoma before chemotherapy from 2004 to 2006. After laboratory preparation, tissue was frozen by a slow cooling technique and stored in liquid nitrogen.
In total 75 women with malignant lymphoma before chemotherapy were referred to our center for consultation--68 chose ovarian inactivation by GnRH analogues during chemotherapy, two IVF cycles with embryo or oocyte cryopreservation and five ovarian tissue cryopreservation. In these five women one to two slices of ovarian cortex from both ovaries were recovered. Totally 20 cryotubes with three pieces of tissue in each were cryopreserved. In no case was metastasis of cancer cells found by histological evaluation.
Cryopreservation of ovarian tissue represents an effective alternative or addition to the cryopreservation of embryos or oocytes for women at risk of premature ovarian failure due to chemotherapy. Reproductive function protection requires close cooperation between oncology departments and assisted reproduction centers.
The study was conducted to compare the presence of cardiotoxicity after the treatment of Hodgkin's disease with the standard ABVD or BEACOPP protocol. We examined 29 patients treated by means of the ...ABVD regimen and 34 treated with the BEACOPP regimen. Using rest echocardiography we assessed the left ventricular function before and after the therapy. One year after the completion of therapy, a control examination was performed with a battery of tests; the rest and dynamic stress echocardiography and cardiopulmonary tests were carried out to assess cardiopulmonary performance. A similar significant deterioration of ejection fraction and diastolic function was apparent after the treatment in both sub-groups with a further progression at the one-year control. Only one patient from the BEACOPP sub-group showed a pathological drop of EF <50%. The most affected parameters of left ventricular function (LV) were Doppler indices. We found a significant relationship of the parameters of LV function compared with age, the cumulative dose of doxorubicin and the cumulative dose of radiotherapy. Multivariate analysis demonstrated that diastolic dysfunction correlated with advanced age and the cumulative dose of doxorubicin, and decreased cardiopulmonary performance with advanced age, radiotherapy, and female gender. Both parameters were significantly influenced by the presence of hypertension. The used regimens demonstrated similar subclinical cardiotoxicity, thus the most aggressive regimen, BEACOPP, is not accompanied by a higher rate of cardiac impairment. The clinical value of such subclinical cardiotoxicity will be estimated in a further prospective follow-up.
The prospective study was conducted to determine whether standard regimen ABVD used in the treatment of Hodgkin's disease is accompanied by the presence of early and chronic myocardial impairment. ...The study comprised 52 patients (30 male and 22 female) aged 34+/-15 years (range 18-71; median 30) with Hodgkin's disease and the control group with 40 healthy volunteers (21 male and 19 female) aged 40+/-8 years (range 20-70; median 38). The maximal administered cumulative dose (CD) of doxorubicin was 297+/-50 mg/m2 (range 150-450; median 300). Radiotherapy of the mediastinum was delivered to 27 (52%) patients with a mean dose 41+/-4 Gy (range 30-46; median 42). Echocardiography was performed at baseline and before each course of chemotherapy. The control examination was done at one month after the treatment and after one year. The stress echocardiography was performed at one-year control. Significant change of ejection fraction (EF) during the treatment was observed only in 10 (18%) patients (7 male/3 female) aged 29+/-13 years (range 18-56; median 22). The mean toxic CD of doxorubicin was 170+/-33 mg/m2 (range 100-200; median 175) and the mean time of the onset EF decline was 13.3+/-3 weeks (range 8-16; median 14). These changes were asymptomatic, and all patients completed the treatment successfully. Four patients (8%) demonstrated significant asymptomatic decline of EF after the chemotherapy. When compared the value of EF after one-year examination, a stable significant decline of EF in the sub-group with early toxicity was found. Despite a difference in the rest EF, the exercise increment of EF did not reveal any significant difference among tested groups and the contractile reserve of the left ventricle in patients was not impaired. The present data shows that the treatment of Hodgkin's disease with the standard ABVD regimen is accompanied with mild early and chronic asymptomatic changes of the left ventricular function. These changes were not reversible during one-year follow-up.
Presentation of clinical results and experience with this technique during past six years.
Original paper.
Gynekologicko-porodnická klinika LF MU a FN Brno, Interní hemato-onkologická klinika LF MU a ...FN Brno, Department of Obstetrics and Gynecology. Hadassah University Hospital Ein-Karem, Jerusalem, Izrael.
Ovarian tissue cryopreservation (OTC) and its future auto-transplantation becomes an alternative for patients to prevent serious damage of ovarian function by oncology treatment.
Patient is indicated to OTC in case of high risk of ovarian failure due to planned chemotherapy and impossibility to use other oncofertility techniques. Ovarian tissue harvesting is done by laparoscopy in short-term general anesthesia. After tissue processing the samples are cryopreserved in programmable automatic freezer or by vitrification. The auto-transplantation of ovarian tissue is planned after the complete cure of patient's malignancy. Our workplace doesn't have own experience with tissue transplantation - until now cryopreserved tissue has not yet been utilized by the patients. Clinical experience with this technique gained by our team during academic stay in abroad Israeli clinic is presented.
During the years of 2005-2011 the OTC was performed in 19 cancer patients before chemotherapy. In majority of cases, patients suffered from blood or lymph node systemic malignancy (84%). Average age of women was 26 years. The patient set consisted of mostly nulliparous women (88%). Patient's average body mass index was 23,9 kg/m2. The length of systemic chemotherapy averaged 7.1 months. Time from fertility preservation counseling to chemotherapy was not exceeding one week (7.2 days on average). Ovarian tissue harvesting was conducted by laparoscopic surgery in all cases. The length of surgery did not exceed 60 minutes and no surgical complications were observed. The case of ovarian tissue transplantation performed on abroad university settings is discussed.
In the consensus of with international guidelines OTC is offered to patients with high risk of ovarian failure doe to cytotoxic oncology treatment. Research in the field of oncofertility is focused on the techniques of in-vitro folliculogenesis in retrieved ovarian tissue.
Infertility is one of the most common permanent implications of oncology treatment of patients in reproductive age. The aim of this paper is to summarize current knowledge about the impact of basic ...modalities of oncology treatment on human reproduction. The authors describe the influence of chemotherapy, radiotherapy and pelvic surgery on the reproductive functions of men and women. Both chemotherapy and radiotherapy diminish the ovarian reserve of follicles, which is the main determining factor of premature ovarian failure. Modern markers of ovarian reserves are introduced, which in common clinical practice can effectively help to evaluate the risk of irreversible damage to the gonadal cells done by oncological disease or its curative treatment. If there is a good chance to permanently cure malignant disease in an oncological patient of fertile age, it is advisable to consider new modern techniques of reproductive protection in cooperation with reproductive medicine specialists.
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