Incidence Of Premature Ovarian Failure Research Articles

Follow-up analysis of sex hormone levels and prognosis in women after hematopoietic stem cell transplantation

Objective: To investigate the levels of sex hormone and fertility in female patients after hematopoietic stem cell transplantation (HSCT), as well as their correlation with conditioning regimens, and analyse the effect of hormone replacement therapy (HRT) in young women after HSCT. Methods: Retrospective case series study. The clinical data of 147 women who underwent HSCT in the First Affiliated Hospital of Soochow University from January 2010 to January 2021 were retrospectively analyzed. The sex hormone levels were measured and followed-up, and the survival, menstrual fertility and the use of HRT of the patients were also followed-up. The sex hormone levels were measured after transplantation, and the ovarian function was evaluated. Independent sample t test and χ2 test were used for comparison between the two groups. Results: The median age of the 147 patients was 26 (range, 10-45) years. Of them, 135 patients received allogeneic HSCT and 12 patients received autologous HSCT. Furthermore, 129 patients received myeloablative conditioning, and 18 patients received reduced conditioning dose. The median follow-up time was 50 months (range, 18-134 months). Five patients died of disease recurrence during follow-up. Of the 54 patients with subcutaneous injection of zoladex, three recovered menstruation spontaneously after transplantation, and all of them were myeloablative conditioning patients, one patient gave birth to twins through assisted reproductive technology. Ninety-three patients did not use zoladex before conditioning, two patients with aplastic anemia with non-myeloablative transplantation resumed menstruation spontaneously, and conceived naturally. The level of follicle stimulating hormone after transplantation in patients receiving myeloablative conditioning regimen was significantly higher than that in patients receiving reduced-dose conditioning regimen [(95.28±3.94) U/L vs. (71.85±10.72) U/L, P=0.039]. Among 147 patients, 122 patients developed premature ovarian failure, 83 patients received sex hormone replacement therapy after transplantation, and 76 patients recovered menstruation and improved endocrine function. Conclusions: The incidence of premature ovarian failure is high in female patients after HSCT, and patients have a chance at natural conception. Reducing the dose of conditioning regimen and the application of zoladex before transplantation can reduce ovarian of conditioning drugs. HRT after transplantation can partially improve the endocrine function of patients.

Analysis of the benefit of gonadotropin-releasing hormone agonist treatment in premenopausal women undergoing hematopoietic cell transplantation

Gonadotropin-releasing hormone agonist (GnRHa) appears to exhibit ovarian protection during chemotherapy for malignant tumors. The purpose of this study was to analyze the benefits of GnRHa in premenopausal women undergoing hematopoietic cell transplantation (HSCT). Candidates for myeloablative chemotherapy HSCT requiring fertility preservation in the Gynecological Endocrinology Clinic of Peking University People’s Hospital from December 2011 to December 2021 were retrospectively analyzed. Patients who chose to receive GnRHa treatment were given at least 2 courses of a 3.75-mg dose of a GnRHa before myeloablative chemotherapy, and patients who chose not to receive GnRHa treatment were included in the control group. All patients were monitored for menstruation return and menopause-related symptoms, and ovarian function tests [follicle-stimulating hormone (FSH), luteinizing hormone, and estradiol] were performed 6–12 months after HSCT. In addition, we assessed the vaginal bleeding of patients in the laminar air-flow room (LAFR). A total of 234 cases were included in this study: 77 cases in the treatment group and 157 cases in the control group. The incidence of vaginal bleeding in the LAFR in the treatment group was significantly lower than that in the control group (24.68% vs. 79.62%, P < 0.001). The menopausal symptoms of the patients in the treatment group were reduced after transplantation (46.75% vs. 19.75%, P < 0.001). There was no difference in visible follicles by follow-up ultrasound in the two groups after HSCT (16.88% vs. 13.38%, P = 0.474). The level of FSH at 6–12 months after transplantation was lower (98.00 mIU/ml vs. 117.53 mIU/ml, P = 0.001). The proportion of patients with FSH < 40 mIU/ml did not differ between the two groups. One patient in the treatment group recovered spontaneous menstruation, while none recovered spontaneous menstruation in the control group (1.30% vs. 0%, P = 0.329). The use of GnRHa may relieve menopause-related symptoms and reduce vaginal bleeding in the LAFR and breakthrough bleeding after transplantation. GnRHa treatment can reduce the level of FSH after myeloablative chemotherapy, but it cannot reduce the incidence of premature ovarian failure in women of reproductive age following myeloablative HSCT.

Epigenetic regulation in premature ovarian failure: A literature review.

Premature ovarian failure (POF), or premature ovarian insufficiency (POI), is a multifactorial and heterogeneous disease characterized by amenorrhea, decreased estrogen levels and increased female gonadotropin levels. The incidence of POF is increasing annually, and POF has become one of the main causes of infertility in women of childbearing age. The etiology and pathogenesis of POF are complex and have not yet been clearly elucidated. In addition to genetic factors, an increasing number of studies have revealed that epigenetic changes play an important role in the occurrence and development of POF. However, we found that very few papers have summarized epigenetic variations in POF, and a systematic analysis of this topic is therefore necessary. In this article, by reviewing and analyzing the most relevant literature in this research field, we expound on the relationship between DNA methylation, histone modification and non-coding RNA expression and the development of POF. We also analyzed how environmental factors affect POF through epigenetic modulation. Additionally, we discuss potential epigenetic biomarkers and epigenetic treatment targets for POF. We anticipate that our paper may provide new therapeutic clues for improving ovarian function and maintaining fertility in POF patients.

Incidence of premature ovarian failure and early menopause in carriers of &lt;i&gt;BRCA1&lt;/i&gt; pathogenic variants

Aim. To determine the incidence of premature ovarian failure (POF) and early menopause with regard to reproductive status in carriers of the pathogenic variant of the BRCA1 gene.&#x0D; Materials and methods. According to the inclusion and exclusion criteria, out of 90 carriers of pathogenic variants of the BRCA1 gene, 38 females were included in the study group, and 110 females without these pathogenic variants were included in the control group. The reproductive status, age of menopause onset, history of pelvic surgeries, and palliative care were evaluated in the study groups.&#x0D; Results. The incidence of POF in the group of carriers of pathogenic variants of the BRCA1 gene was significantly higher compared to the control group (p0.004), while the incidence of early menopause showed no significant differences in the studied groups (13.2% vs. 4.5%, respectively; p0,069). No significant differences were found in the analysis of reproductive status.&#x0D; Conclusions. Females with and without pathogenic variants of the BRCA1 gene did not differ significantly by the main indices of reproductive status. Carriers of pathogenic BRCA1 gene variants have a significantly higher incidence of POF vs. controls. Adverse effects of pathogenic BRCA gene variants on women's ovarian reserve and reproductive potential cannot be excluded. Healthy carriers of pathogenic variants of the BRCA1/2 gene are recommended to plan pregnancy in the early reproductive period.

Effect of human umbilical cord mesenchymal stem cells on ovarian function in lupus mice

AbstractBackgroundPatients with systemic lupus erythematosus (SLE) suffer from a high incidence of premature ovarian failure, which might be due to cyclophosphamide gonadal toxicity, immune abnormalities, or other reasons. This study aimed to investigate whether the transplantation of human umbilical cord mesenchymal stem cells (HUC‐MSCs) can improve ovarian reserve function in lupus mice.MethodsWe used MRL/lpr mice to observe changes in ovarian structure and secretory function in SLE. Lupus mice and controls were injected with HUC‐MSCs at Weeks 12 and 16. We detected serum concentrations of the sex hormones estradiol (E2), follicle‐stimulating hormone (FSH), and anti‐Müllerian hormone (AMH), using enzyme‐linked immunosorbent assays. Hematoxylin and eosin staining showed ovarian tissue structure and enabled the counting of follicles. Hepatocyte growth factor (HGF) and insulin‐like growth factor 1 (IGF‐1) expression in ovarian tissue was observed by immunohistochemistry.ResultsOvarian function in lupus mice was abnormal, as indicated by decreased serum E2 and AMH concentrations, and increased FSH concentrations. HUC‐MSC transplantation caused significant upregulation of serum E2 and AMH and downregulation of FSH (all p &lt; 0.05). Ovarian structure improved and the follicle number increased after HUC‐MSC transplantation. Multiple infusions of HUC‐MSCs at Weeks 12 and 16 resulted in a significantly higher number of primordial follicles than infusions of HUC‐MSCs at only Week 12 (p &lt; 0.05). Immunohistochemistry showed that IGF‐1 and HGF expression increased after HUC‐MSC transplantation, but this was not significant.ConclusionsHUC‐MSCs transplantation restores disturbed hormone secretion and folliculogenesis in lupus mice. HUC‐MSC transplantation should be repeated for the best treatment effect.

Application and Mechanism of Action of Zuogui Pill in the Treatment of Premature Ovarian Failure

The incidence of premature ovarian failure is increasing year by year, which brings serious harm to women's physical and mental health. Western medicine is mostly based on hormone replacement therapy, which may increase the risk factor for vaginal bleeding and endometrial cancer with long-term use. According to Traditional Chinese Medicine, the treatment of premature ovarian failure is based on kidney tonification and treatment according to the evidence. Zuogui Pill can regulate immune factors and reproductive endocrine function, inhibit rapid apoptosis of granulosa cells, promote angiogenesis, increase local blood supply, thereby improving ovarian function, regulating menstrual status, and alleviating perimenopausal syndrome. However, a standardized and comprehensive treatment system needs to be explored in depth.

Research Progress on the Treatment of Premature Ovarian Failure Using Mesenchymal Stem Cells: A Literature Review

Premature ovarian failure (POF) has become one of the main causes of infertility in women of childbearing age and the incidence of POF is increasing year by year, seriously affecting the physical and mental health of patients and increasing the economic burden on families and society as a whole. The etiology and pathogenesis of POF are complex and not very clear at present. Currently, hormone replacement therapy is mainly used to improve the symptoms of low estrogen, but cannot fundamentally solve the fertility problem. In recent years, stem cell (SC) transplantation has become one of the research hotspots in the treatment of POF. The results from animal experiments bring hope for the recovery of ovarian function and fertility in patients with POF. In this article, we searched the published literature between 2000 and 2020 from the PubMed database (https://pubmed.ncbi.nlm.nih.gov), and summarized the preclinical research data and possible therapeutic mechanism of mesenchymal stem cells (MSCs) in the treatment of POF. Our aim is to provide useful information for understanding POF and reference for follow-up research and treatment of POF.

A Preliminary Study on the Mechanism of Premature Ovarian Failure

Premature ovarian failure (POF) refers to the failure of ovaries which causes amenorrhea before the age of 40. It is characterized by primary or secondary amenorrhea along with elevated blood gonadotropin levels and decreased estrogen levels with varying degrees of low estrogen symptoms such as hot flashes and sweating, facial flushing, reduced libido, and so on. Premature ovarian failure (POF) is a common endocrine disease in gynecology. The incidence of POF is increasing year by year and the affected population increasingly involves the younger-aged groups. Its etiology is complex and diverse involving many factors such as genetics, immunity, medical treatment, environment endocrine disruptors, etc. It is also affected by long-term smoking, alcohol intake, and other behaviors which damage patients’ physical and mental health. In recent years, the effects of gene therapy in restoring ovarian function and improving fertility in animal experiments have provided a new direction for POF patients. This article discusses the etiology and possible pathogenesis of POF and BRCA from various aspects as well as summarizes the recent research status and progress of new treatment methods of POF.

EFFECT OF PLATELET-RICH PLASMA IN CYCLOPHOSPHAMIDE-INDUCED OVARIAN FAILURE IN ALBINO RATS: HISTOLOGICAL AND ANATOMICAL STUDY

Amenorrhea and ovarian disorders are a common concern of women under the age of 40, a condition medically known as premature ovarian failure (POF). The incidence of POF among Egyptian women before the age of 40, is about 8% that exceeds the global incidence which is about 1%. Chemotherapeutic agents were linked to toxicity of ovarian tissues and disturbance of ovarian functions. Provision of a suitable protective agent with high efficacy, low side effects and cost is a major challenge in the field of oncofertility. Aim of the study: is to evaluate the mechanism of PRP treatment in induced ovarian failure due to cyclophosphamide.Materials and methods: The present study was carried out on twenty-nine albino rats. Twenty-four adult female albino rats were used as the experimental group. Five age-matched healthy male albino rats were used to get the PRP. The twenty-four adult female albino rats were randomly assigned into three groups (control, group II: received cyclophosphamide, group III: received cyclophosphamide and PRP). Plasma estradiol and progesterone levels were measured on day 22 after cyclophosphamide treatment before experimental rats euthanasia. The rats were euthanized and ovaries were anatomically examined using dissecting stereomicroscope. Sections of the ovaries were prepared and examined histologically, immunohistochemicaly and using transmission electron microscope.Results: Cyclophosphamide treated groups showed signs of degeneration of follicles and oocyte and deterioration of ovarian functions. PRP treated group showed improved appearance of ovarian follicles and improved ovarian functions. Conclusion: PRP seems to have protective effects on ovarian tissues and functions and its concomitant use with cyclophosphamide helps to restore the ovarian tissues.

CORRELATION BETWEEN PLASMA LEAD AND SERUM ANTI MULLERIAN HORMONE LEVELS IN WOMEN WITH PREMATURE OVARIAN FAILURE

Background: Lead is a highly toxic metal to humans, with the injurious effects on the hemopoietic, nervous and reproductive system. Lead crosses the placenta during pregnancy and has been associated with intrauterine death, prematurity and low birth weight. Objective: To collate between plasma lead and serum antimullerian hormone levels in women with premature ovarian failure, by estimation of level of Anti Mullerian Hormone (AMH), Follicular Stimulating Hormone (FSH), Estradiol (E2) and plasma Lead level. Subjects and Method: This study was conducted in Al Azhar University Hospital outpatient clinics after approval of the research and ethical committee during the period from December 2015 to December 2018. Study groups were: Group 1 included 50 normal candidate women under 40 years old has regular menstrual cycles (21-35 days), fertile (at least one natural pregnancy carried to term), and serum FSH was less than 10 mlU/ml, Group 2 included 50 patients with premature ovarian failure who aged under 40 years with absence of spontaneous menstrual bleeding for more than 12 months, serum estradiol level was less than 25pg/ml, serum FSH level more than 40 mlU/ml. AMH, plasma lead level in patients with premature ovarian failure diagnosed and correlated with level of serum FSH with the normal control group. Results: There was a statistically significant positive correlation between plasma lead levels with FSH among the study group. On the other hand, there was no statistically significant correlation between plasma lead level and AMH level. Conclusion: The anti mullerian hormone showed a significant difference between the cases of premature ovarian insufficiency and the control group. Moreover, AMH was a good marker for ovarian reserve and ovarian response for gonadotropins simulation. Chronic exposures to heavy metals, especially lead, affected the ovarian function and impairment in folliculogenesis which increased the incidence of Premature Ovarian Failure (POF) especially in rural area due to the low socioeconomic status.

CORRELATION BETWEEN PLASMA LEAD AND SERUM ANTI MULLERIAN HORMONE LEVELS IN WOMEN WITH PREMATURE OVARIAN FAILURE

Background: Lead is a highly toxic metal to humans, with the injurious effects on the hemopoietic, nervous and reproductive system. Lead crosses the placenta during pregnancy and has been associated with intrauterine death, prematurity and low birth weight. Objective: To collate between plasma lead and serum antimullerian hormone levels in women with premature ovarian failure, by estimation of level of Anti Mullerian Hormone (AMH), Follicular Stimulating Hormone (FSH), Estradiol (E2) and plasma Lead level. Subjects and Method: This study was conducted in Al Azhar University Hospital outpatient clinics after approval of the research and ethical committee during the period from December 2015 to December 2018. Study groups were: Group 1 included 50 normal candidate women under 40 years old has regular menstrual cycles (21-35 days), fertile (at least one natural pregnancy carried to term), and serum FSH was less than 10 mlU/ml, Group 2 included 50 patients with premature ovarian failure who aged under 40 years with absence of spontaneous menstrual bleeding for more than 12 months, serum estradiol level was less than 25pg/ml, serum FSH level more than 40 mlU/ml. AMH, plasma lead level in patients with premature ovarian failure diagnosed and correlated with level of serum FSH with the normal control group. Results: There was a statistically significant positive correlation between plasma lead levels with FSH among the study group. On the other hand, there was no statistically significant correlation between plasma lead level and AMH level. Conclusion: The anti mullerian hormone showed a significant difference between the cases of premature ovarian insufficiency and the control group. Moreover, AMH was a good marker for ovarian reserve and ovarian response for gonadotropins simulation. Chronic exposures to heavy metals, especially lead, affected the ovarian function and impairment in folliculogenesis which increased the incidence of Premature Ovarian Failure (POF) especially in rural area due to the low socioeconomic status.

Cryptotanshinone decreases granulosa cell apoptosis and restores ovarian function in mice with premature ovarian failure.

With the increasing incidence of premature ovarian failure (POF) seriously threaten the women's health. Whether cryptotanshinone decreased the granulosa cell apoptosis to improve the POF would be explored. POF mice were conducted with intraperitoneal injection of cyclophosphamide and then treated with cryptotanshinone. The body weight and ovarian weight were recorded. The estrus was detected by vaginal smears. The pathological changes of ovarian were observed with hematoxylin and eosin staining. ELISA assay analyzed the levels of LH, FSH, AMH, E2 and AzpAB in mice serum. The expression of Bcl-2, Bax, KI67 and PCNA in ovarian tissues was detected by Western blot analysis and KI67 expression was also determined by immunohistochemistry. The body weight and ovarian weight were decreased and the pathological results of ovarian were worsen in POF mice. The estrus was decreased in POF mice. The levels of LH, FSH and AzpAB were increased and the levels of AMH and E2 were decreased in POF mice serum. The expression of Bcl-2, KI67 and PCNA was decreased and Bax expression was increased in ovarian tissues of POF mice. Those changes affected by cyclophosphamide could be reversed by cryptotanshinone. Cryptotanshinone could decrease the granulosa cell apoptosis to restore ovarian function.

Adjuvant gonadotropin-releasing hormone analogues for the prevention of chemotherapy-induced premature ovarian failure in premenopausal women.

Adjuvant gonadotropin-releasing hormone analogues for the prevention of chemotherapy-induced premature ovarian failure in premenopausal women.

Transplantation of Human Menstrual Blood Stem Cells to Treat Premature Ovarian Failure in Mouse Model

The incidence of premature ovarian failure (POF), also known as ovarian insufficiency, has been increasing in recent years. Although some treatments are currently available, improved treatment strategies are urgently required. Many researchers have reported that human endometrial stem cells (HuMenSCs), which exhibit stem/progenitor cell properties in vitro repaired damaged cells in vivo. Thus, we aimed to determine whether HuMenSCs can serve as cell therapy tools and be used for the treatment of POF. After treating with cyclophosphamide, on the first estrus period (we predicted mouse estrus cycle was generally 5 days), HuMenSCs were injected into a cyclophosphamide-induced mouse model of POF. The results revealed that the HuMenSCs could survive within POF mouse ovaries for at least 14 days in vivo; further, ovaries of the HuMenSCs-transplanted group expressed higher levels of ovarian markers [AMH, inhibin α/β, and follicle-stimulating hormone receptor (FSHR)], and the proliferative marker Ki67. In addition, the ovarian weight, plasma E2 level, and the number of normal follicles increased over time in the HuMenSC group compared with the control group. Further, microarray analysis of cDNA expression patterns revealed that, after HuMenSC transplantation, the gene mRNA expression patterns in the ovarian cells following stimulation of the host ovarian niche became increasingly similar to those observed in human ovarian tissue compared with the pretransplantation mRNA expression pattern in HuMenSCs. Hence, we can safely conclude that the mesenchymal stem cell properties and in vivo survival of HuMenSCs make them ideal seed cells for stem cell transplantation in the treatment of POF.

Induction of Estrogen-Sensitive Epithelial Cells Derived from Human-Induced Pluripotent Stem Cells to Repair Ovarian Function in a Chemotherapy-Induced Mouse Model of Premature Ovarian Failure

The incidence of premature ovarian failure (POF), a condition causing amenorrhea and hypergonadotropic hypoestrogenism in women before the age of 40, has been increasing in recent years. As an irreversible pathological change, improved treatment strategies for this disease are urgently needed. In this study, a type of microRNA (miR-17-3p) was used to guide the differentiation of human-induced pluripotent stem (iPS) cells into hormone-sensitive ovarian epithelial (OSE)-like cells in vitro. To prevent their morphological transformation into fibroblast-like cells, MiR-17-3p, a microRNA that suppresses vimentin expression, was transfected into human iPS cells. Subsequently, these cells were successfully induced into OSE-like cells in vitro after treatment with estrogen and cell growth factors. Compared with controls, iPS cells transfected with miR-17-3p expressed higher levels of epithelial markers (cytokeratin 7, AE1, AE3, and E-cadherin) and estrogen receptors (ERα and ERβ) while levels of mesenchymal markers (fibronectin, vimentin, and N-cadherin) lowered after the induction. The human iPS cell-derived OSE-like cells were then injected into cyclophosphamide-induced POF model mice to determine their potential benefit as grafts to repair ovarian tissues. The OSE-like cells survived within POF mouse ovaries for at least 14 days in vivo. Compared with the negative controls, expressions of cytokeratin 7 and ERβ proteins were elevated while fibronectin and vimentin levels in ovarian tissues were downregulated in the OSE-like cell transplantation group. Moreover, the ovarian weight and plasma E2 level increased over time in the transplantation with OSE-like cells, compared with control groups. Hence, we can draw the conclusion that iPS cells can be induced to differentiate into OSE-like cells in vitro.

Oral Cyclophosphamide Confounds the Relationship between CYP2C19 and CYP2B6 Pharmacogenetics and Cyclophosphamide-induced premature Ovarian Failure in Lupus Nephritis Patients

Cyclophosphamide treatment of lupus nephritis is associated with ovarian toxicity. Four separate studies have previously demonstrated a lower risk of cyclophosphamide induced premature ovarian failure (POF) in carriers of the CYP2C19*2 null function allele. This hepatic enzyme bioactivates cyclophosphamide. CYP2B6 is also important in the activation of this prodrug however, genetic variants of CYP2B6 have not been associated with POF risk. The aim of this study was to determine the relationship between CYP2C19 and CYP2B6 loss of function variants and prevalence of ovarian toxicity following treatment with monthly pulses of intravenous cyclophosphamide in lupus nephritis patients. In 28 pre-menopausal female patients, there was a 25% incidence of POF. In contrast to previous studies of a similar size we could not detect a significant relationship between the risk of POF and genetic variants of CYP2C19, alone or in combination with variants of CYP2B6. However, 71.4% of the cases with POF had been treated with additional daily oral cyclophosphamide compared with only 4.7% of controls (P < 0.02; OR 14.29 (95% CI, 1.4-144.5). Thus the effect of daily oral cyclophosphamide administration in addition to pulsed intravenous monthly doses may have obscured any protective effect of CYP2C19 loss of function in this cohort.

Two successful pregnancies in a patient with chemotherapy-induced ovarian failure while on hormone replacement therapy

Chemotherapeutic agents administered for the treatment of malignancies can result in the incidence of premature ovarian failure (POF). Ovarian failure is reflected by elevated serum follicle-stimulating hormone (FSH) levels that may reach menopausal levels, at which the chances of a pregnancy are considered extremely rare. We report a case of a 26-year-old female who experienced two successful pregnancies, despite her diagnosis with chemotherapy-induced POF. This case suggests that patients who suffer from POF secondary to chemotherapy might still retain enough ovarian function with good quality oocytes that could support a healthy pregnancy.

Gonadotropin-releasing hormone analog cotreatment for preservation of ovarian function during gonadotoxic chemotherapy: a systematic review and meta-analysis

To determine whether gonadotropin-releasing hormone (GnRH) analog cotreatment with chemotherapy provides better reproductive outcomes for women at risk of premature ovarian failure (POF) as a side-effect of gonadotoxic chemotherapy. Systematic review and meta-analysis. University-affiliated research centers. None. Electronic and manual searches (e.g., MEDLINE, EMBASE, CENTRAL) up to January 2010 were performed to identify randomized controlled trials (RCTs) comparing GnRH cotreatment with chemotherapy alone in premenopausal women. Incidence of POF after treatment, incidence of women with resumption of ovulation, POF after an initial normal cycle, normal cycles but abnormal markers of ovarian reserve, spontaneous occurrence of pregnancy after treatment, and time to reestablishment of menstruation; data also extracted to allow for an intention-to-treat analysis. Twenty-eight RCTs were identified, but only six met the inclusion criteria. Data were only available for the incidence of women with new onset of POF, resumption of ovulation, and occurrence of pregnancy. The incidence of POF or resumption of ovulation both demonstrated a statistically significant difference in favor of the GnRH cotreatment. The occurrence of spontaneous pregnancy showed no statistically significant difference between GnRH cotreatment and the control groups. Evidence from RCTs suggests a potential benefit of GnRH cotreatment with chemotherapy in premenopausal women, with higher rates of spontaneous resumption of menses and ovulation but not improvement in pregnancy rates. Data relating to study quality and possible bias for the majority of the outcomes in this review were not available, denoting possible selective reporting of trial data.

The OPTION trial of adjuvant ovarian protection by goserelin in adjuvant chemotherapy for early breast cancer.

590 Background: Nonrandomised studies suggest that goserelin may protect the ovaries against chemotherapy induced premature menopause. The primary objective of the open, randomised multicentre OPTION trial was to determine the impact of goserelin on the incidence of premature ovarian failure following chemotherapy for operable breast cancer. Secondary objectives were to record menstruation (diary) and pregnancies, assess quality of life (FACT-ES) and menopausal symptoms, and measure changes in bone mineral density (BMD) and bone turnover markers, hormone levels (including AMH and inhibin B). Methods: All premenopausal ER negative women (or ER positive women for whom ovarian suppression was not considered necessary) planned for adjuvant or neoadjuvant chemotherapy, were considered for inclusion. Women were stratified by age >/ = 40 or < 40 years at randomisation, and by centre. Chemotherapy regimens comprised any 6-8 cycles of chemotherapy containing cyclophosphamide and/or anthracycline. Regimens could include taxanes. Goserelin was randomly allocated to start before or at first chemotherapy cycle and continued 3-4 weekly to final cycle. For the purposes of the sample size calculation, the rates of premature menopause were assumed to be 40% in the under 40 age group and 80% in the over 40 age group (Bines et al, J Clin Oncol 14(5):1718-29 1996). Reported rates of preservation of ovarian function using goserelin with chemotherapy in uncontrolled studies are around 80%, (possibly higher in the under 40's): i.e. rates of premature menopause with goserelin of around 20% or less. Based on a one sided test with 5% false positive rate, the groups required approximately 140 and 70 patients respectively to have a 80% chance of detecting an absolute reduction in premature menopause rate of 20% and 25% respectively, that is from 40% to 20% in the under 40 age group and from 80% to 55% in the over 40 age group. A total of 210 patients were therefore required. Results: At trial closure, 31/12/09, 227 patients had been randomised. Conclusions: The primary accrual endpoint of more than 210 patients has been achieved and so we expect the statistical requirements to be met. Primary and selected secondary endpoints will be presented. No significant financial relationships to disclose.

Phase II study of gonadotropin-releasing hormone analogue for ovarian function preservation in hematopoietic stem cell transplantation patients.

9025 Background: The incidence of premature ovarian failure (POF) in patients received conventional chemotherapy alone ranges from 40%-70%. However, the incidence increases to 70%-100% in patients ...