trelstar and Primary-Ovarian-Insufficiency

It is still controversial that GnRH agonist (GnRHa) protects ovarian function from chemotherapy-induced gonadotoxicity. Indeed, the results of many studies related to this issue are neither consistent nor convincing because of the weak study design and the inadequate sample size. We identified 11 prospective controlled studies (8 nonrandomized and 3 randomized) for the systemic review and meta-analysis. The meta-analysis showed that GnRHa cotreatment during chemotherapy can protect ovarian function. However, it is worthy to note that the result of this meta-analysis is influenced by nonrandomized studies. The protective effect of GnRHa will remain elusive until the currently ongoing large, prospective, randomized studies are completed. In addition, tamoxifen, a selective estrogen receptor modulator, may have the protective effect against loss of follicles and ovarian function, which was caused by chemotherapy.

Topics: Animals; Antineoplastic Agents; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Menstruation; Neoplasms; Ovary; Primary Ovarian Insufficiency; Randomized Controlled Trials as Topic; Tamoxifen; Triptorelin Pamoate

Decreased secretion of pituitary gonadotropins, by decreasing gonadal function, may possibly protect against the sterilizing effects of chemotherapy. Although previous claims that primordial germ cells fare better than germ cells that are part of an active cell cycle have been made, this hypothesis has not been seriously tested clinically until recently. The only prospective randomized study performed to date found that gonadotropin releasing hormone agonistic analogue (GnRH-a) protected the ovary against cyclophosphamide-induced damage in Rhesus monkeys by significantly decreasing the number of follicles lost during the chemotherapeutic insult. We have administered a monthly depot i.m. injection of GnRH-a to more than 125 young patients exposed to gonadotoxic chemotherapy for malignant or nonmalignant diseases, after informed consent, starting before chemotherapy for up to 6 months, in parallel and until the end of chemotherapeutic treatment. Less than 7% developed irreversible hypergonadotropic amenorrhea. The remainder (>93%) resumed cyclic ovarian function, of which 32 patients spontaneously conceived 46 times. These patients were compared to a control group of over 125 patients of comparable age (15-40 years), who were similarly treated with chemotherapy but without the GnRH-a adjuvant. The 2 groups were similar in age, diagnosis, and the ratio of HD to non-Hodgkin lymphoma patients. The 2 groups also received similar doses of radiotherapy exposure and the proportion of radio-plus chemotherapy-treated patients was similar. The cumulative doses of each chemotherapeutic agent and the mean or median radiotherapy exposure did not differ between the groups. Our and others' results support the effectiveness of GnRH-a administration also to patients receiving cyclophosphamide pulses for systemic lupus erythematosus and other autoimmune diseases. Possible explanations for the beneficial effect of the GnRH-a on minimizing the gonadotoxic effect of chemotherapy are discussed. Multi-center prospective, randomized studies are awaited to substantiate the in vivo effect of GnRH-a as an unequivocal means of minimizing follicular apoptosis.

Topics: Adolescent; Adult; Animals; Antineoplastic Agents; Autoimmune Diseases; Azoospermia; Clinical Trials as Topic; Cohort Studies; Combined Modality Therapy; Cyclophosphamide; Embryo Transfer; Female; Fertilization in Vitro; Germ Cells; Gonadotropin-Releasing Hormone; Hematologic Neoplasms; Hodgkin Disease; Humans; Infertility, Female; Infertility, Male; Lymphoma, Non-Hodgkin; Macaca mulatta; Male; Mice; Ovary; Pregnancy; Pregnancy Outcome; Primary Ovarian Insufficiency; Radiotherapy; Sex Characteristics; Triptorelin Pamoate

The investigational endeavors of ovarian cryopreservation await the clinical experience of auto- or xenotransplantation, in vitro maturation of thawed primordial follicles, their in vitro fertilization and embryo transfer. Although promising, this experience is not yet available. Moreover, the risk of possible reimplantation of malignant stem cells with the thawed cryoperserved ovary has been raised following experimental animal observations. Therefore, until these innovative endeavors prove successful, we have attempted to minimize the gonadotoxic effect of chemotherapy by the co-treatment with a gonadotropin-releasing hormone agonistic analog (GnRH-a) to induce a temporary prepubertal milieu. The immunoreactive inhibin-A and -B in these patients was measured before, during and following the gonadotoxic chemotherapy.. A prospective clinical protocol was undertaken in 60 women aged 15-40 years with lymphoma, 10 with leukemia and 10 undergoing chemotherapeutic treatments for non-malignant diseases such as systemic lupus erythematosus or other autoimmune diseases. A monthly injection of depot D-TRP(6)-GnRH-a was administered from before starting the chemotherapy until its conclusion, up to a maximum of 6 months. Hormonal profile [follicle-stimulating hormone (FSH), luteinizing hormone (LH), E2, T, P4, insulin-like growth factor (IGF)-1, IGF-BP3 and prolactin) was taken before starting the GnRH-a/chemotherapy co-treatment, and monthly thereafter until resumtion of spontaneous ovulation. This group was compared with a control group of 60 women who have been treated with similar chemotherapy.. Whereas all but three (40, 36 and 34 year old) of the surviving patients within the GnRH-a/ chemotherapy co-treatment group resumed spontaneous ovulation and menses within 12 months, less than half of the patients in the 'control' group (chemotherapy without GnRH-a co-treatment) resumed ovarian function and regular cyclic activity (P <0.05). The remaining 55% experienced premature ovarian failure (POF). Temporarily increased FSH concentrations were experienced by about one-third of the patients resuming cyclic ovarian function, suggesting reversible ovarian damage in a larger proportion of women than those experiencing POF. Inhibin-A and -B decreased during the GnRH-a/ chemotherapy co-treatment but increased to normal levels in patients who resumed regular ovarian cyclicity, and/or spontaneously conceived, as compared with low levels in those who developed POF.. If these preliminary data are consisent in a larger group of patients, GnRH-a co-treatment should be considered in every woman of reproductive age receiving chemotherapy, in addition to assisted reproductive technologies and the investigation into ovarian cryopreservation for future in vitro maturation, autotransplantation or xenotransplantation.

Topics: Adolescent; Adult; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Cryopreservation; Female; Fertility; Hodgkin Disease; Humans; Inhibins; Organ Preservation; Ovary; Ovum; Primary Ovarian Insufficiency; Triptorelin Pamoate

We have reported previously that after 1-year follow up, gonadotropin-releasing hormone agonist (GnRHa) did not prevent chemotherapy-induced premature ovarian failure (POF) in patients with lymphoma, but may provide protection of the ovarian reserve. Here, we report the final analysis of the cohort after 5 years of follow up.. A total of 129 patients with lymphoma were randomly assigned to receive either triptorelin plus norethisterone (GnRHa group) or norethisterone alone (control group) during chemotherapy. Ovarian function and fertility were reported after 2, 3, 4, and 5 to 7 years of follow up. The primary end point was POF, defined as at least one follicle-stimulating hormone value of > 40 IU/L after 2 years of follow up.. Sixty-seven patients 26.21 ± 0.64 years of age had available data after a median follow-up time of 5.33 years in the GnRHa group and 5.58 years in the control group (P = .452). Multivariate logistic regression analysis showed a significantly increased risk of POF in patients according to age (P = .047), the conditioning regimen for hematopoietic stem cell transplant (P = .002), and the cumulative dose of cyclophosphamide > 5 g/m(2) (P = .019), but not to the coadministration of GnRHa during chemotherapy (odds ratio, 0.702; P = .651). The ovarian reserve, evaluated using anti-Müllerian hormone and follicle-stimulating hormone levels, was similar in both groups. Fifty-three percent and 43% achieved pregnancy in the GnRHa and control groups, respectively (P = .467).. To the best of our knowledge, this is the first long-term analysis confirming that GnRHa is not efficient in preventing chemotherapy-induced POF in young patients with lymphoma and did not influence future pregnancy rate. These results reopen the debate about the drug's benefit in that it should not be recommended as standard for fertility preservation in patients with lymphoma.

Topics: Adult; Female; Fertility; Fertility Preservation; Gonadotropin-Releasing Hormone; Humans; Lymphoma; Middle Aged; Norethindrone; Ovary; Primary Ovarian Insufficiency; Prospective Studies; Triptorelin Pamoate

To determine the dose of triptorelin that is sufficient to maintain complete ovarian suppression in female patients with childhood-onset systemic lupus erythematosus (SLE) who require cyclophosphamide therapy, to determine the length of time needed to achieve ovarian suppression after initiation of triptorelin treatment, and to investigate the safety of triptorelin.. In this randomized, double-blind, placebo-controlled, dose-escalation study, female patients ages <21 years were randomized 4:1 to receive triptorelin (n = 25) or placebo (n = 6). The starting doses of triptorelin were 25, 50, 75, and 100 μg/kg, and the dose was escalated until complete ovarian suppression was maintained. The primary outcome was the weight-adjusted dose of triptorelin that provided complete ovarian suppression in at least 90% of the patients, as determined by gonadotropin-releasing hormone agonist stimulation testing. The secondary outcome was the period of time required to achieve ovarian suppression, as measured by unstimulated follicle-stimulating hormone and luteinizing hormone levels after the initiation of triptorelin treatment.. Treatment with triptorelin at a weight-adjusted dose of 120 μg/kg body weight provided sustained complete ovarian suppression in 90% of the patients. After administration of the initial dose of triptorelin, 22 days were required to achieve complete ovarian suppression. The rates of adverse events (AEs) and serious adverse events (SAEs) per 100 patient-months of followup were not higher in the triptorelin group compared with the placebo group (for AEs, 189 versus 362; for SAEs, 2.1 versus 8.5).. High doses of triptorelin are needed to achieve and maintain complete ovarian suppression, but such doses appear to be well tolerated in adolescent female patients with childhood-onset SLE. Our data suggest that a lag time of 22 days after initiation of triptorelin treatment is required before cyclophosphamide therapy is started or continued.

Topics: Adolescent; Antirheumatic Agents; Cyclophosphamide; Double-Blind Method; Female; Follicle Stimulating Hormone; Humans; Lupus Erythematosus, Systemic; Luteinizing Hormone; Luteolytic Agents; Ovulation Inhibition; Primary Ovarian Insufficiency; Time Factors; Triptorelin Pamoate; Young Adult

To assess the efficacy of gonadotropin-releasing hormone agonist (GnRHa) in preventing chemotherapy-induced ovarian failure in patients treated for Hodgkin or non-Hodgkin lymphoma within the setting of a multicenter, randomized, prospective trial.. Patients age 18 to 45 years were randomly assigned to receive either the GnRHa triptorelin plus norethisterone (GnRHa group) or norethisterone alone (control group) concomitantly with alkylating agents containing chemotherapy. The primary end point was the premature ovarian failure (POF) rate (follicle-stimulating hormone [FSH] ≥ 40 IU/L) after 1 year of follow-up.. Eighty-four of 129 randomly assigned patients completed the 1-year follow-up. The mean FSH values were higher in the control group than in the GnRHa group during chemotherapy; however, this difference was no longer observed after 6 months of follow-up. After 1 year, 20% and 19% of patients in the GnRHa and control groups, respectively, exhibited POF (P = 1.00). More than half of patients in each group completely restored their ovarian function (FSH < 10 IU/L), but the anti-Müllerian hormone values were higher in the GnRHa group than in the control group (1.4 ± 0.35 v 0.5 ± 0.15 ng/mL, respectively; P = .040). The occurrence of adverse events was similar in both groups with the exception of metrorrhagia, which was more frequently observed in the control group than the GnRHa group (38.4% v 15.6%, respectively; P = .024).. Approximately 20% of patients in both groups exhibited POF after 1 year of follow-up. Triptorelin was not associated with a significant decreased risk of POF in young patients treated for lymphoma but may provide protection of the ovarian reserve.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Drug Therapy, Combination; Estradiol; Female; Follicle Stimulating Hormone; Follow-Up Studies; Gonadotropin-Releasing Hormone; Hodgkin Disease; Humans; Luteolytic Agents; Lymphoma; Lymphoma, Non-Hodgkin; Middle Aged; Norethindrone; Premenopause; Primary Ovarian Insufficiency; Prospective Studies; Time Factors; Treatment Failure; Triptorelin Pamoate

Premenopausal patients with breast cancer are at high risk of premature ovarian failure induced by systemic treatments, but no standard strategies for preventing this adverse effect are yet available.. To determine the effect of the temporary ovarian suppression obtained by administering the gonadotropin-releasing hormone analogue triptorelin during chemotherapy on the incidence of early menopause in young patients with breast cancer undergoing adjuvant or neoadjuvant chemotherapy.. The PROMISE-GIM6 (Prevention of Menopause Induced by Chemotherapy: A Study in Early Breast Cancer Patients-Gruppo Italiano Mammella 6) study, a parallel, randomized, open-label, phase 3 superiority trial, was conducted at 16 sites in Italy and enrolled 281 patients between October 2003 and January 2008. The patients were premenopausal women with stage I through III breast cancer who were candidates for adjuvant or neoadjuvant chemotherapy. Assuming a 60% rate of early menopause in the group treated with chemotherapy alone, it was estimated that 280 patients had to be enrolled to detect a 20% absolute reduction in early menopause in the group treated with chemotherapy plus triptorelin. The intention-to-treat analysis was performed by including all randomized patients and using imputed values for missing data.. Before beginning chemotherapy, patients were randomly allocated to receive chemotherapy alone or combined with triptorelin. Triptorelin was administered intramuscularly at a dose of 3.75 mg at least 1 week before the start of chemotherapy and then every 4 weeks for the duration of chemotherapy.. Incidence of early menopause (defined as no resumption of menstrual activity and postmenopausal levels of follicle-stimulating hormone and estradiol 1 year after the last cycle of chemotherapy).. The clinical and tumor characteristics of the 133 patients randomized to chemotherapy alone and the 148 patients randomized to chemotherapy plus triptorelin were similar. Twelve months after the last cycle of chemotherapy (last follow-up, August 18, 2009), the rate of early menopause was 25.9% in the chemotherapy-alone group and 8.9% in the chemotherapy plus triptorelin group, an absolute difference of -17% (95% confidence interval, -26% to -7.9%; P < .001). The odds ratio for treatment-related early menopause was 0.28 (95% confidence interval, 0.14 to 0.59; P < .001).. The use of triptorelin-induced temporary ovarian suppression during chemotherapy in premenopausal patients with early-stage breast cancer reduced the occurrence of chemotherapy-induced early menopause.. clinicaltrials.gov Identifier: NCT00311636.

Topics: Adult; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cisplatin; Female; Fluorouracil; Goserelin; Humans; Infertility, Female; Injections, Intramuscular; Luteolytic Agents; Menopause; Methotrexate; Middle Aged; Neoadjuvant Therapy; Premenopause; Primary Ovarian Insufficiency; Tamoxifen; Triptorelin Pamoate

To minimize the gonadotoxic effect of chemotherapy by the cotreatment with a GnRH agonistic analogue (GnRH-a).. Prospective nonrandomized study with concurrent and historical controls.. University medical center.. One hundred fifteen female patients with Hodgkin lymphoma (HL).. Sixty-five patients received a monthly injection of GnRH-a, administered before starting chemotherapy until its conclusion, up to a maximum of 6 months. Thirty-five patients were treated with ABVD and 76 with a procarbazine-containing regimen. This group was compared with a control group of 46 women who were treated concurrently with similar chemotherapy (n = 26) without GnRH-a or were historical controls (n = 20).. Cyclic ovarian function (COF) versus premature ovarian failure (POF).. The ovarian function could be determined in 111 patients. In the GnRH-a/chemotherapy group, 63 out of 65 patients resumed ovulation and regular menses (96.9 %), compared with 63% of the 46 control subjects. Twenty of the 22 patients in the BEACOPP/escalated BEACOPP/GnRH-a cotreatment resumed cyclic ovarian function versus 9 of the 14 in the chemotherapy-only group. All 17 MOPP/ABV/GnRH-a cotreated patients resumed COF versus 11 of the 22 in the chemotherapy-only group. There was no significant effect of the GnRH-a cotreatment regarding COF in the ABVD group. There were no significant differences in the cumulative doses of the various alkylating agents between the two groups.. Cotreatment with GnRH-a may reduce ovarian damage significantly in female patients treated for HL and should be considered in addition to assisted reproduction for women in reproductive age receiving gonadotoxic chemotherapy.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Hodgkin Disease; Humans; Injections; Menstrual Cycle; Ovary; Pregnancy; Pregnancy Rate; Primary Ovarian Insufficiency; Time Factors; Treatment Outcome; Triptorelin Pamoate

In young women receiving chemotherapy for Hodgkin's disease, the combined use of triptorelin and tibolone cotreatment may be a useful tool for preserving ovarian function because all but three (10%) of the women in this treatment group returned to spontaneous ovulation and menses, in contrast to 23% of subjects in the control group (P<.05). No significant differences were observed in bone mineral density between groups.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Density; Cyclophosphamide; Dacarbazine; Doxorubicin; Female; Gonadotropin-Releasing Hormone; Hodgkin Disease; Humans; Norpregnenes; Ovary; Prednisone; Primary Ovarian Insufficiency; Procarbazine; Triptorelin Pamoate; Vinblastine; Vincristine

We have evaluated the best method to assess the ovarian reserve and the ovarian protective effect of GnRH-analog (GnRH-a), in 29 women with Hodgkin's disease (HD) treated with chemotherapy (CHT). The ovarian reserve was studied by measuring the serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), inhibin B, antimullerian hormone (AMH) and the ultrasound antral follicular count (AFC). The patients were randomly treated with or without GnRH-a. At the time of study menstrual function was normal in 21 cases (72.4%), but absent in 8 (27.5%). Mean basal values of FSH, LH, AMH, inhibin B and AFC were normal in patients less than 30 years old and in the group treated four years or less before observation. AFC appeared to be the best marker of reduced ovarian reserve and a combination of AFC-AMH or inhibin B appeared the best predictor. In the GnRH-a group, no women had amenorrhoea, although ovarian reserve assessment was not significantly different from those who were not treated. The time-interval from CHT was the only significant predictor of ovarian function in GnRH-a treated patients. In conclusion, ovarian reserve evaluation, in young patients treated by CHT, can be performed by AFC. GnRH-a treatment does not have a protective effect, but could delay the development of ovarian failure.

Topics: Adolescent; Adult; Amenorrhea; Anti-Mullerian Hormone; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dacarbazine; Dexamethasone; Doxorubicin; Female; Follicle Stimulating Hormone; Glycoproteins; Hodgkin Disease; Humans; Infertility, Female; Inhibins; Luteinizing Hormone; Mechlorethamine; Ovarian Follicle; Ovary; Predictive Value of Tests; Prednisolone; Prednisone; Primary Ovarian Insufficiency; Procarbazine; Sensitivity and Specificity; Survivors; Testicular Hormones; Time Factors; Triptorelin Pamoate; Ultrasonography; Vinblastine; Vincristine

To determine if gonadotropin suppression improves ovarian follicle function or ovulation rates in patients with karyotypically normal spontaneous premature ovarian failure.. Prospective, double-blind, placebo-controlled, crossover trial.. Tertiary care research institution.. Two intervention phases lasting 4 months each: one placebo phase, and one treatment phase during which each patient received daily subcutaneous injections of 300 micrograms of the gonadotropin-releasing hormone agonist (GnRH-a) deslorelin. During both phases, patients took a standardized estrogen (E) replacement regimen.. Twenty-six patients with karyotypically normal spontaneous premature ovarian failure ranging in age from 18 to 39 years.. We measured serum estradiol (E2) and progesterone (P) levels weekly during the 2 months after each intervention. We defined a serum E2 greater than 50 pg/mL (184 pmol/L) as evidence for ovarian follicle function and a serum P greater than 3.0 ng/mL (9.5 nmol/L) as evidence for ovulation.. The GnRH-a therapy did not significantly enhance recovery of ovarian follicle function or the chance of ovulation. The power to detect a 40% and a 33% ovulation success rate with therapy was 0.95 and 0.83, respectively. We found evidence for ovarian follicle function in 11 of 23 women (48%), and 4 women (17%) ovulated.. Patients with karyotypically normal spontaneous premature ovarian failure treated with E replacement did not benefit from the additional gonadotropin suppression achieved with GnRH-a. Because these patients have a significant possibility of spontaneous remission, attempts to induce ovulation should be limited to controlled trials designed to determine safety and effectiveness.

Topics: Adult; Double-Blind Method; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Injections, Subcutaneous; Karyotyping; Primary Ovarian Insufficiency; Progesterone; Prospective Studies; Triptorelin Pamoate

Cyclophosphamide (CP) is a chemotherapy alkylating agent that causes a lot of side effects including premature ovarian failure (POF). This study aimed to evaluate the possible protective effect of fenofibrate (FEN) in CP-induced POF. Rats were randomly divided into five groups as follows: negative control, CP, triptorelin (TRI)-treated, FEN (FEN)-treated, and FEN + TRI-treated. Histological study, collagen area fraction, and immunoexpression of proliferating cell nuclear antigen (PCNA) were evaluated. Also, estrogen, anti-mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and ovarian malondialdehyde (MDA), nitric oxide (NOx), reduced glutathione (GSH), superoxide dismutase (SOD), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor (VEGF) were measured. CP significantly reduced ovarian follicle count, as compared with the control group (1.00 ± 0.76 versus 7.75 ± 1.83, respectively). Meanwhile, FEN, either solely or in combination with TRI, significantly increased ovarian follicle count, as compared with the CP group (3.88 ± 0.83 and 5.75 ± 1.39, respectively). As compared with the control group, CP increased the levels of MDA, NOx, IL-10, TNF-α, FSH, LH, and collagen area fraction; however, levels of GSH, SOD, VEGF, AMH, estrogen, and PCNA immunoexpression were reduced with CP. Administration of FEN either solely or in combination with TRI showed significant improvement in all the parameters previously mentioned. FEN can protect the ovary from CP-induced side effects possibly through antioxidant and anti-inflammatory actions.

Topics: Animals; Antineoplastic Agents; Cyclophosphamide; Drug Combinations; Drug Therapy, Combination; Female; Fenofibrate; Glutathione; Hormones; Interleukin-10; Malondialdehyde; Nitrites; Ovary; Oxidative Stress; Primary Ovarian Insufficiency; Protective Agents; Rats, Wistar; Superoxide Dismutase; Triptorelin Pamoate; Tumor Necrosis Factor-alpha

Cyclophosphamide treatment has been associated with ovarian function impairment. Co-treatment with gonadotropin-releasing hormone-analogue (GnRH-a) seems to be able to prevent this complication. However, even though data are available on neoplastic patients, limited data have been published on systemic lupus erythematosus (SLE) women cohorts.. To evaluate GnRH-a efficacy on ovarian function preservation in SLE women receiving cyclophosphamide treatment.. The authors performed a retrospective study including SLE women requiring cyclophosphamide treatment and compared those treated with and without GnRH-a (case and controls, respectively). All patients were evaluated before cyclophosphamide treatment and every 3 months in the following years. Ovarian function was evaluated using hormonal profiles.. The study comprised 33 SLE cyclophosphamide-treated women: 18 co-treated with triptorelin and 15 controls. The mean follow-up was 8.1 ± 5.1 years (range 4-11). Premature ovarian failure (POF) prevalence was significantly lower in SLE women treated by cyclophosphamide plus triptorelin compared to controls (11.1% vs. 33.3%, P = 0.0002). The occurrence of POF was significantly associated with higher age at the time of cyclophosphamide treatment (P = 0.008). Only patients in the GnRH-a treated group had successful pregnancies.. The study provides information about the efficacy of co-treatment with GnRH-a in SLE women receiving cyclophosphamide, as demonstrated by the lower POF incidence compared to untreated subjects, based on long-term follow-up. These results reinforce the use of GnRH-a for fertility preservation in premenopausal SLE patients treated by cyclophosphamide.

Topics: Adult; Cyclophosphamide; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Lupus Erythematosus, Systemic; Primary Ovarian Insufficiency; Retrospective Studies; Time Factors; Triptorelin Pamoate

Triptorelin, a gonadotropin releasing hormone analogue, can be administered to postpubertal female individuals with cancer who receive chemotherapy to obtain menstrual suppression and decrease the risk of hemorrhage caused by thrombocytopenia. Our goal was to assess whether triptorelin also has a protective role against the gonadotoxicity of chemotherapy.. This retrospective observational study includes all postmenarchal female patients who presented to our Unit from 2000 to 2015 and received chemotherapy for cancer. They were administered depot triptorelin. We evaluated long-term ovarian function in order to detect clinical signs of ovarian damage, miscarriages, and pregnancies. Laboratory follow-up consisted in dosing serum follicle stimulating hormone, luteinizing hormone, prolactin, estradiol, and progesterone. Ultrasound of the ovaries was performed as well.. Of 36 evaluable patients, 9 received hematopoietic stem cell transplantation (HSCT). The remaining 27 patients maintained normal ovarian function at clinical, laboratory, and ultrasound assessment. Five of them achieved spontaneous physiological pregnancy. Four of the 9 patients who underwent HSCT developed premature ovarian failure.. Our study suggests that gonadotropin releasing hormone-a administered during chemotherapy can prevent premature ovarian failure in patients treated without HSCT and that it is not enough to preserve the ovarian function during HSCT. Hence, a prospective randomized trial with a larger population would be recommended.

Topics: Adolescent; Antineoplastic Agents; Child; Estradiol; Female; Fertility Preservation; Follicle Stimulating Hormone; Follow-Up Studies; Humans; Luteinizing Hormone; Neoplasms; Ovary; Primary Ovarian Insufficiency; Progesterone; Prolactin; Retrospective Studies; Triptorelin Pamoate

This study analyzes our single-center, retrospective experience on 63 premenopausal breast cancer patients treated with monthly triptorelin and concomitant chemotherapy.. Concomitant chemotherapy and triptorelin were adopted as part of premature ovarian failure prevention strategy.. Age at diagnosis was the main factor influencing fertility preservation (p = 0.002). Compared with patients aged 41-45 years, the probability of menses resumption was almost threefold than for women aged 35-40 years, and significantly higher for women aged <35 years (hazard ratio: 9.0; p = 0.0001). The cumulative proportion among patients who resumed menses was 33.3% at 6 months, 75% at 12 months and 87.5% at 24 months. Seven patients attempted pregnancy, and five (71%) obtained healthy deliveries.. We observed an acceptable rate of fertility preservation. Age at diagnosis influences fertility preservation.

Topics: Adult; Age Factors; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Female; Fertility Preservation; Follow-Up Studies; Humans; Middle Aged; Pregnancy; Premenopause; Primary Ovarian Insufficiency; Retrospective Studies; Treatment Outcome; Triptorelin Pamoate

Topics: Antineoplastic Combined Chemotherapy Protocols; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Lymphoma; Premenopause; Primary Ovarian Insufficiency; Triptorelin Pamoate

Topics: Antineoplastic Combined Chemotherapy Protocols; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Lymphoma; Premenopause; Primary Ovarian Insufficiency; Triptorelin Pamoate

To evaluate the possible protective effect of low and high dose of triptorelin, a GnRH analogue, on cyclophosphamide-induced ovarian toxicity in adult female mice.. Thirty-six sexually mature, virgin, female mice were divided randomly into six groups of six each: control group, low-dose triptorelin (TL) group, high-dose triptorelin (TH) group, cyclophosphamide (CPA) group, low-dose triptorelin plus cyclophosphamide (TL + CPA) group and high-dose triptorelin plus cyclophosphamide (T + CPA) group. Mice in both the TL + CPA and the TH + CPA groups were injected with 3.8 and 38 mg/kg of triptorelin subcutaneously, respectively. Four weeks later, mice in the CPA, TL + CPA and TH + CPA groups were injected with cyclophosphamide, intraperitoneally, at a dose of 50 mg/kg. Ovaries were removed 4 weeks later and processed for light microscopic examinations.. Obvious destruction of ovarian structure and significant depletion of primordial, primary, secondary and antral follicles were demonstrated in the CPA group and compared with the control group, the difference was statistically highly significant (p < 0.001), affirming the ovarian toxicity of cyclophosphamide. In the TL + CPA group, there was a significant increase in primordial, primary, secondary and antral follicles compared with the CPA group (p < 0.05), showing the effect of triptorelin on ovarian protection. Regarding, the high-dose GnRH agonist the difference was statistically highly significant for primordial and primary follicles (p < 0.001).. This study has showed a dose-dependent protective effect of GnRH analogue on ovarian reserve against ovarian toxic chemotherapy, thus demonstrating an important role of GnRH analogues in fertility preservation.

Topics: Animals; Antineoplastic Agents, Alkylating; Cyclophosphamide; Dose-Response Relationship, Drug; Female; Fertility Preservation; Gonadotropin-Releasing Hormone; Mice; Ovary; Primary Ovarian Insufficiency; Triptorelin Pamoate

Topics: Antineoplastic Agents; Antineoplastic Agents, Hormonal; Biomarkers; Chorionic Gonadotropin; Endocrinology; Estrogens; Female; Fertility Agents, Female; Humans; Middle Aged; Obesity; Ovarian Neoplasms; Pregnancy; Pregnancy, Ectopic; Primary Ovarian Insufficiency; Reproductive Medicine; Triptorelin Pamoate; Weight Reduction Programs

To compare the rate of premature ovarian failure (POF) after stem cell transplantation (SCT) in young women receiving GnRH-agonist (GnRH-a) in conjunction with gonadotoxic chemotherapy.. Prospective, nonrandomized study.. Tertiary university hospital.. Ninety-five women received conditioning chemotherapy, with or without GnRH-a before SCT. Complete information was available for only 83 patients.. Conditioning chemotherapy, with or without GnRH-a before SCT.. Cyclic ovarian function (COF) or POF after SCT.. There were no significant differences in age, chemotherapy treatment, or diagnoses between the study and control groups. In the GnRH-a group, 38.3% (18/47) patients resumed COF, compared with 11.1% (4/36) for patients who did not receive GnRH-a. Patients who resumed COF were on average 3.7 years (median, 3 years) younger at the time of transplantation than those who experienced POF. GnRH-a had a significant effect on long-term COF in patients with lymphomas (66.7% [14/21] for GnRH-a group vs. 18.2% [2/11] for control) but not for leukemia patients.. GnRH-a cotreatment in conjunction with conditioning chemotherapy before SCT may significantly decrease the gonadotoxicity and POF from 82% to 33% in lymphoma but not in leukemia patients.

Topics: Adult; Case-Control Studies; Chi-Square Distribution; Female; Fertility Agents, Female; Fertility Preservation; Gonadotropin-Releasing Hormone; Humans; Israel; Leukemia; Lymphoma; Ovary; Primary Ovarian Insufficiency; Prospective Studies; Risk Assessment; Risk Factors; Stem Cell Transplantation; Time Factors; Transplantation Conditioning; Treatment Outcome; Triptorelin Pamoate

Topics: Adult; Antineoplastic Agents; Breast Neoplasms; Female; Humans; Infertility, Female; Luteolytic Agents; Middle Aged; Premenopause; Primary Ovarian Insufficiency; Triptorelin Pamoate

Topics: Antineoplastic Agents; Breast Neoplasms; Female; Humans; Infertility, Female; Luteolytic Agents; Menopause; Primary Ovarian Insufficiency; Triptorelin Pamoate

To demonstrate the protective effect of triptorelin, a GnRH analogue, on chemotherapy-induced ovarian gonadotoxicity.. Twenty-four sexually mature, virgin, female FVB/NJNarl mice were divided into four groups: busulfan (B); low-dose triptorelin plus busulfan (T(L)+B); high-dose triptorelin plus busulfan (T(H)+B); and control. Mice in the T(L)+B and T(H)+B groups were injected with 3.8 and 38 mg/kg of triptorelin subcutaneously, respectively. Four weeks later, mice in the B, T(L)+B, and T(H)+B groups were injected with busulfan intraperitoneally at a dose of 36 mg/kg. Histologic examinations were performed 4 weeks later.. Obvious destruction of ovarian structure and significant depletion of primordial, primary, and secondary follicles were demonstrated in the B group compared with the control group, affirming the gonadotoxicity of busulfan. In the T(L)+B group, a greater number of larger primordial and primary follicles were enumerated compared with the B group; however, statistical significance was not achieved. In the T(H)+B group, the number of primordial and primary follicles was significantly greater than in the B group, and the ovarian tissue in the T(H)+B group was spared, demonstrating the effect of triptorelin pre-treatment on ovarian protection.. Our results have demonstrated a dose-dependent protective effect against gonadotoxic chemotherapy of a GnRH analogue on ovarian reserve, thus suggesting a novel application of GnRH analogues in fertility preservation.

Topics: Animals; Antineoplastic Agents; Busulfan; Female; Gonadotropin-Releasing Hormone; Mice; Ovarian Follicle; Ovary; Primary Ovarian Insufficiency; Triptorelin Pamoate

Topics: Adolescent; Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Female; Fertility Agents, Female; Hodgkin Disease; Humans; Menstrual Cycle; Pregnancy; Pregnancy Rate; Primary Ovarian Insufficiency; Treatment Outcome; Triptorelin Pamoate

Many patients who receive co-treatment with GnRH agonists (GnRH-a) during chemotherapy treatment preserve their ovarian function and are at risk of unintended pregnancies. Therefore, it is important to offer them effective contraception. Also, pregnancies occurring after cancer therapy in women who received GnRH-a are not associated with adverse neonatal outcomes.

Topics: Adolescent; Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Case-Control Studies; Dacarbazine; Doxorubicin; Female; Gonadotropin-Releasing Hormone; Hematologic Neoplasms; Humans; Infant, Newborn; Middle Aged; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Pregnancy, Unplanned; Primary Ovarian Insufficiency; Time Factors; Triptorelin Pamoate; Vinblastine; Young Adult

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.. 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.. 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.. Study showed a significant reduction of ovarian failure risk in women with HL treated with less aggressive CHT regimens plus a GnRH analogue.

Topics: Adolescent; Adult; Case-Control Studies; Drug Therapy; Female; Follicle Stimulating Hormone; Hodgkin Disease; Humans; Luteinizing Hormone; Luteolytic Agents; Ovary; Primary Ovarian Insufficiency; Treatment Outcome; Triptorelin Pamoate

We conducted a retrospective study on treatment-related ovarian failure in 61 women with Hodgkin lymphoma who were under treatment from 1994 to 2006. To minimize the risk of treatment-related gonadotoxicity, triptorelin (Decapeptyl), a gonadotropin-releasing hormone analog (GnRHa), was administered monthly. All patients were treated with frontline polychemotherapy with or without radiotherapy. Seven refractory or relapsed patients received salvage treatment, and six of these patients further received peripheral blood stem cell transplantation. Fifty patients (82%) recovered regular menses, four patients (6%) reported menstrual abnormalities, and seven patients (12%) who were under salvage treatment became amenorrheic. We found a clear correlation between age at the time of treatment, advanced disease, cumulative therapeutic load and ovarian failure. After the completion of treatment, 13 patients who attempted conception conceived. GnRHa may preclude ovarian damage and infertility in young women receiving frontline polychemotherapy alone or in combination with supradiaphragmatic radiotherapy. In refractory or relapsed patients, GnRHa does not seem to be very effective, and further experimental approaches are required for fertility preservation.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Female; Hodgkin Disease; Humans; Infertility, Female; Luteolytic Agents; Neoplasm Recurrence, Local; Peripheral Blood Stem Cell Transplantation; Primary Ovarian Insufficiency; Reproduction; Retrospective Studies; Salvage Therapy; Triptorelin Pamoate

Premature ovarian failure (POF) can be considered a consequence of chemotherapy performed in patients affected by oncohematological disease. The aim of this study was to evaluate the administration of GnRh analogs (aGnRh) to prevent gonadal toxicity associated with cancer treatment.. From April 1996 to May 2002 a total of 49 fertile women affected by oncohematological diseases (Hodgkin's lymphoma, non-Hodgkin's lymphoma, acute leukemia) and treated with chemotherapy were evaluated. Ovarian function was studied through a 40.7 month observation period, after chemotherapy, in 3 different groups: women treated with aGnRh, oral contraceptives treatment and no preventive-treatment. The differences in these groups as to menstrual cycle, blood ovarian hormones, age at diagnosis, type and dosage of chemotherapy administered were evaluated. Statistical analysis was performed by chi2 test with Yates correction and Fisher test.. All patients treated with aGnRh and chemotherapy achieved a good ovarian function. A normal ovarian function was also obtained in 75% of patients treated with oral contraceptives and only in 59.3% of women with no preventive treatment. Significant difference was found comparing aGnRh group with no preventive-treatment group (P<0.05). No significant differences were found between other groups.. Use of GnRh analogs administered before beginning chemotherapy prevents from gonadal damage in all cases observed. Higher chemotherapy toxicity and older age at diagnosis time decrease ovarian function.

Topics: Adolescent; Adult; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Contraceptives, Oral; Female; Gonadotropin-Releasing Hormone; Hematologic Neoplasms; Humans; Longitudinal Studies; Middle Aged; Primary Ovarian Insufficiency; Prospective Studies; Triptorelin Pamoate

Infertility represents one of the main sequelae of cytotoxic therapy given for various malignant diseases. Because dividing cells are more sensitive to cytotoxic effects than are cells at rest, it has been hypothesized that inhibition of the pituitary-gonadal axis may facilitate the preservation of future gonadal function. The aim of our study was to find a quick, reliable and economic way to suppress the pituitary-gonadal axis by combining GnRH-agonists with GnRH-antagonists in order to preserve future gonadal function.. A combination of D-Trp6-GnRH-a (3.75 mg) and cetrorelix (3 mg) was used to achieve a quick downregulation in six postmenarchal young women (aged 15.4 +/- 0.7) years with haematological malignancies before the onset of cytotoxic chemotherapy.. The combination of D-Trp6-GnRH-a and GnRH-antagonist cetrorelix induced a reliable and long-lasting suppression of gonadotrophin secretion within 96 hours in all patients allowing cytotoxic therapy to be started without any delay.. The combination of GnRH-agonist and GnRH-antagonist enables a rapid, reliable and cost-effective suppression of the pituitary-gonadal axis to be achieved. Future gonadal function of treated patients will be monitored.

Topics: Adolescent; Antineoplastic Agents; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Luteinizing Hormone; Primary Ovarian Insufficiency; Prospective Studies; Triptorelin Pamoate

A combination of gonadotropin-releasing hormone agonist and human menopausal gonadotropins was used for ovulation induction in a patient with premature ovarian failure. A paradoxical suppression of any ovarian response was noted despite increasing doses of human menopausal gonadotropins.

Topics: Adult; Delayed-Action Preparations; Drug Therapy, Combination; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Luteinizing Hormone; Menotropins; Ovulation Induction; Primary Ovarian Insufficiency; Triptorelin Pamoate