GnRH Agonist Administration Research Articles

Effectiveness of basal LH in monitoring central precocious puberty treatment in girls.

Treatment of central precocious puberty (CPP) is based on administration of GnRH agonists in order to suppress hypothalamic-pituitary-gonadal axis and thus induce the stabilization or regression of pubertal development. Our aim was to determine whether the single basal serum LH and/or FSH concentration could be an effective tool to assess the efficacy of treatment to suppress activation of hypothalamic-pituitary axis. Serum LH and FSH were measured before and after the GnRH injection, as well as E2 basal levels in 60 girls with documented idiopathic CPP at diagnosis and 18 and 30 months after the beginning of therapy. At diagnosis, peaks of >5IU/L of LH and of FSH were observed in 100 and 91.6% of girls, respectively, with basal LH values of <1IU/L in 70% and basal FSH levels of <1IU/L in 10%. E2 were <20pg/mL in 36.6%. After 18 months, a suppressed peak (i.e. <3IU/L) was recorded in 85% of girls (p<0.01) for LH and in 98.3% for FSH (p<0.01). Basal LH <1IU/L was detected in 85% (p<0.01) and basal FSH ≤1IU/L in 40% (p<0.01). Serum E2 ≤20pg/mL was recorded in 61.6% (p<0.01). After 30 months, all patients showed LH suppressed peak (p<0.01) and 98.3% suppressed FSH peak (p<0.01). 100% showed basal LH concentrations <1IU/L (p<0.01) and 38.3% FSH basal values <1UI/mL (p<0.01). E2 ≤20pg/mL was observed in 32.72% (p=NS). Basal LH values are a reliable indicator of the efficacy of GnRHa therapy after 30 months of GnRHa therapy.

Use of GnRH analogue in the endometriosis recurrence after surgery

: Endometriosis recurrence after surgery is still an issue that afflicts the gynecologist. Adjuvant hormonal treatments have been suggested and approved in order to delay recurrence in symptoms and endometriotic lesions. The current review analyzes the impact of postoperative gonadotropin-releasing hormone agonists administration on the recurrence rate of endometriosis. We selected randomized controlled trials on this topic. The reported findings are controversial and the definition of recurrence varies among the sources. The emerging results report that the postoperative administration of gonadotropin-releasing hormone agonists seems beneficial on symptoms control and it delays the subjective recurrence (although it is related to the known side effects), but the duration of the post-operative treatment plays an important role.

Comparison of effect of preoperative dienogest and gonadotropin-releasing hormone agonist administration on laparoscopic cystectomy for ovarian endometriomas.

To compare the effects of preoperative dienogest (DNG) and gonadotropin-releasing hormone (GnRH) agonist administration on the improvement of preoperative symptoms and surgical outcomes in patients who underwent laparoscopic cystectomy for ovarian endometriomas. Seventy patients who were scheduled for laparoscopic surgery were enrolled in the study. They were divided into two groups: 35 patients who received DNG for 4months preoperatively (group D) and 35 patients who received low-dose sustained-release goserelin acetate for 4months preoperatively (group G). Preoperative outcomes, including pain score associated with endometriosis, using the numerical rating scale (NRS), adverse events of hormonal therapy and Kupperman index (KI) before and after treatment, surgical outcomes including total surgical duration and blood loss, and postoperative recurrence of endometrioma were compared between the two groups. Regarding preoperative symptoms, NRS and KI at 4months after preoperative hormonal therapy were significantly lower in group D than in group G (NRS, 5.3 ± 5.5 vs. 2.7 ± 3.9; P = 0.01; KI, 16.0 ± 11.0 vs. 9.2 ± 7.6; P = 0.006). Regarding adverse events, the incidence of hot flashes was significantly lower in group D than in group G (P < 0.001). Meanwhile, the incidence of breast pain and metrorrhagia was significantly higher in group D than in group G (P = 0.04 and P < 0.001, respectively). The total surgical duration and blood loss were not significantly different between the groups. At 12months after surgery, ovarian endometrioma did not recur in either group. Preoperative administration of DNG is more valuable for patients with endometriosis and scheduled for laparoscopic surgery to improve symptoms with good efficacy and tolerability than the administration of GnRH agonist.

Effects of gonadotropin-releasing hormone agonist (GnRH-a) as luteal phase support in intracytoplasmic sperm injection (ICSI) cycles: a randomized controlled trial

BackgroundThis paper describes a blind randomized controlled trial (RCT) designed to evaluate the effect of gonadotropin-releasing hormone agonist (GnRH-a) administration on outcomes of intracytoplasmic sperm injection (ICSI) in subjects stimulated with the gonadotropin-releasing hormone (GnRH) antagonist protocol. A total of 268 women who underwent ICSI cycles with GnRH antagonist ovarian stimulation protocol were included in the study. Patients were randomly assigned to the intervention (GnRH-a) and control groups. The intervention group received a single dose injection of triptorelin (0.1 mg) subcutaneously 6 days after oocyte retrieval while the control group received placebo. The rates of chemical and clinical pregnancy were defined as the primary outcome values.ResultsTwo hundred forty participants accomplished the study, and their data were analyzed. No significant difference was detected between the chemical pregnancy rates of the intervention and control groups. However, the clinical pregnancy rate was significantly higher in the GnRH-a group than in the placebo group.ConclusionsThe findings of the present study suggest that the GnRH-a support in the luteal phase can result in a significant improvement of pregnancy rates in ICSI cycles following the ovarian stimulation with GnRH antagonist protocol.

Pituitary apoplexy induced by gonadotropin-releasing hormone agonist administration: a rare complication of prostate cancer treatment.

SummaryGonadotropin-releasing hormone (GnRH) agonists, currently used in the treatment of advanced prostate cancer, have been described as a rare cause of pituitary apoplexy, a potentially life-threatening clinical condition. We report the case of a 69-year-old man with a known pituitary macroadenoma who was diagnosed with prostate cancer and started treatment with GnRH agonist leuprorelin (other hormones were not tested before treatment). Few minutes after drug administration, the patient presented with acute-onset severe headache, followed by left eye ptosis, diplopia and vomiting. Pituitary MRI revealed tumor enlargement and T1-hyperintense signal, compatible with recent bleeding sellar content. Laboratory endocrine workup was significant for low total testosterone. The patient was managed conservatively with high-dose steroids, and symptoms significantly improved. This case describes a rare phenomenon, pituitary apoplexy induced by GnRH agonist. We review the literature regarding this condition: the pathophysiological mechanism involved is not clearly established and several hypotheses have been proposed. Although uncommon, healthcare professionals and patients should be aware of this complication and recognize the signs, preventing a delay in diagnosis and treatment.Learning points:Pituitary apoplexy (PA) is a potentially life-threatening complication that can be caused by gonadotropin-releasing hormone agonist (GnRHa) administration for the treatment of advanced prostate cancer.This complication is rare but should be taken into account when using GnRHa, particularly in the setting of a known pre-existing pituitary adenoma.PA presents with classic clinical signs and symptoms that should be promptly recognized.Patients should be instructed to seek medical care if suspicious symptoms occur.Healthcare professionals should be aware of this complication, enabling its early recognition, adequate treatment and favorable outcome.

Adult height after gonadotropin-releasing hormone agonist treatment in girls with early puberty: A meta-analysis.

This analysis of previously published reports was performed to examine the effects of gonadotropin-releasing hormone (GnRH) agonist treatment on adult height and the factors associated with adult height outcomes. GnRH agonists are first-line agents in the treatment of precocious puberty. However, studies regarding the treatment effect on subjects with early puberty have reported inconsistent results. A total of 14 studies identified from a search of electronic databases (AMED, EMBASE, MEDLINE and RISS) were included. Controlled studies with girls who developed puberty before 10years of age and measurements of the adult heights of the subjects were selected. Studies using only long-acting GnRH agonists to suppress puberty were included. Adult height, duration of the treatment, age at the start of treatment and bone age advancement were analysed. The mean age of the subjects ranged from 6.3 to 9.0years. The meta-analysis showed a pooled mean difference in adult height of 3.2cm and a 95% confidence interval of 1.3-5.1cm. The height difference between the treated subjects and controls was significantly associated with the duration of treatment (P=.005) rather than the age at the start of treatment (P=.084) or the difference between bone age and chronological age (P=.427). Administration of GnRH agonists in girls who develop early puberty and demonstrate advanced bone age may be effective for increasing adult height, especially if a sufficiently long treatment duration can be achieved.

MON-239 Pituitary Apoplexy Induced by Gonadotropin-Releasing Hormone Agonist Administration: A Rare Complication of Prostate Cancer Treatment

Background: Pituitary apoplexy is a potentially life-threatening clinical condition associated with bleeding and/or infarction into the pituitary gland, usually within a tumor. Gonadotropin-releasing hormone (GnRH) agonists, currently used in the treatment of advanced prostate cancer, have been described in the literature as a rare cause of pituitary apoplexy. Case: We report the case of a 69 year-old man with a known pituitary macroadenoma incidentally detected in 2016, without further investigation. He was diagnosed with prostate cancer in 2017 and underwent retropubic prostatectomy. Two years later there was evidence of histologic prostate tumor progression, so he started treatment with leuprorelin 45mg (GnRH agonist). Immediately after the first subcutaneous injection he presented with acute-onset severe headache, followed by left eye ptosis, diplopia and vomiting. Left cranial nerve III palsy was confirmed by examination in the emergency department. Head computed tomography showed a lesion in the sellar region; laboratory endocrine workup was significant for total testosterone 72.07 ng/dL (86.49 – 788.22), with no other abnormalities. Magnetic resonance imaging of the pituitary revealed tumor enlargement and a T1-hyperintense signal, compatible with recent haemorrhagic sellar content. The patient was managed conservatively with high dose steroids, and symptoms were significantly improved on discharge. Discussion: Pituitary apoplexy induced by GnRH agonist administration is a rare complication, described in only 20 documented cases to date. The pathophysiologic mechanism involved is not clearly established and several hypotheses have been proposed: a combination of metabolic hyperactivity, cell division/tumor growth and increased intrasellar pressure, inducing ischemia in a poorly perfused adenomatous tissue given the demand. Although uncommon, healthcare professionals should be aware of this serious consequence of GnRH agonist administration and recognize the signs, preventing a delay in diagnosis and treatment.

An assessment of the protective effect of gonadotropin-releasing hormone agonist and antagonist on bleomycin-induced ovarian toxicity in rats

The aim of this study is to evaluate the effect of GnRH agonist or GnRH antagonist therapy on bleomycin-administered rats by examining ovarian follicle counts and AMH levels. A total of 30 female Wistar albino rats aged 4–6 months were randomly divided into 4 groups. First, an intramuscular injection of bleomycin (30 mg/m2) was administered to all except the control group on the 1st, 8th and 15th days. The control group (Group I) was administered 0.1 mL intramuscular saline on those days. The bleomycin group (Group II) was followed up without any further treatment. The bleomycin + GnRH agonist group (Group III) was administered subcutaneous GnRH agonist triptorelin (1 mg/kg) at the same time as the bleomycin injections. The bleomycin + GnRH antagonist group (Group IV) was administered 1 mg/kg cetrorelix acetate subcutaneously, concurrently with the bleomycin. Although AMH levels were lower in the bleomycin group than in all the other groups, there was no statistically significant difference between the groups in terms of AMH levels (p > .05). In the bleomycin + cetrorelix acetate and bleomycin + triptorelin groups, significantly higher primordial, secondary and tertiary follicle counts were determined compared to the bleomycin group (p < .001). In conclusion the harmful effects of bleomycin on ovarian reserve can be reduced by the simultaneous administration of GnRH agonist or GnRH antagonist.

Ultralong administration of gonadotropin-releasing hormone agonists before in vitro fertilization improves fertilization rate but not clinical pregnancy rate in women with mild endometriosis: a prospective, randomized, controlled trial

To evaluate the effects of gonadotropin-releasing hormone agonists (GnRH-a) on fertility in women with mild endometriosis who are undergoing invitro fertilization and embryo transfer (IVF-ET) procedures. Prospective, randomized, controlled trial. Three tertiary university hospitals. Four hundred infertile women with mild endometriosis, documented with laparoscopy, undergoing IVF and 200 women with tubal factor infertility. Administration of GnRH-a for 3 months before an IVF attempt (group A, n = 200) or IVF without GnRH-a (group B, n = 200). Follicular fluid (FF) levels of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8, and IL-1 receptor antagonist; fertilization rate (FR), implantation rate (IR), quality of embryos, and clinical pregnancy rate (PR). Women who received GnRH-a had a statistically significantly reduced concentration of FF cytokines compared with women who did not receive this regimen. Women in group B had a reduced FR (61.7; 95% CI, 59.20-64.20) compared with the women in group A (72.7; 95% CI, 70.50-74.90) and compared with the women with tubal factor infertility (74.7; 95% CI, 72.00-77.24). The embryo quality, IR, and clinical PR showed no statistically significant improvement in the women of group A compared with group B. Women who received GnRH-a for 3 months had a lower concentration of FF cytokines. These women had also a higher FR than the women who did not receive GnRH-a. However, the IR, embryo quality, and clinical PR showed no statistically significant difference when comparing the two groups. CLINICALTRIALS. NCT01269125.

REPRODUCTIVE FUNCTION AND ANTITUMOR ACTIVITY: DIFFERENT ROLES FOR THE HYPOTHALAMIC HORMONE GnRH

The decapeptide GnRH (Gonadotropin-Releasing Hormone), whose amino acidic sequence was discovered by Dr. A.V. Schally, was initially identified as the key hypothalamic hormone involved in the control of reproductive functions. GnRH, by binding to specific receptors (GnRH-R) at the pituitary level, stimulates the synthesis and secretion of the two gonadotropins (LH, luteinizing hormone and FSH, follicle stimulating hormone) and the downstream production of steroid hormones at the gonadal level. At present, these receptors represent the molecular targets of the standard pharmacological treatments for hormone-related tumors, such as androgen-dependent prostate cancer. Actually, chronic administration of synthetic GnRH agonists induces the desensitization of pituitary receptors and, subsequently, the suppression of testicular androgen production. The physiological role of GnRH in reproductive functions, and its regulation, represented a very important line of research for professor Martini and His colleagues. In the last three decades it has become increasingly clear that GnRH-R are expressed also in a wide range of tumors, both related and unrelated to the reproductive system; in particular GnRH-R are expressed in prostate cancers after development of resistance to androgen ablation therapy (castration resistant prostate cancer, CRPC), a tumor known to be refractory to standard chemotherapy. Activation of these receptors by means of GnRH agonists is associated with a significant antiproliferative/antimetastatic/antiangiogenic activity. These different biological effects at pituitary vs. prostate tissues are related to specific intracellular signal transduction pathways. Based on these observations, tumor GnRH-R are presently considered an effective molecular target for novel therapies (‘targeted’ therapies). In particular, GnRH-based bioconjugates, in which a standard cytotoxic drug is linked to a GnRH analog, have been developed. The rationale for this ‘targeted’ therapy is that the GnRH analog behaves as the targeting moiety by binding to GnRH-R in tumors, thus specifically delivering (targeting) the cytotoxic drug to tumor cells. At the level of tumor cells, the bioconjugate is internalized and degraded at the lysosomal level; in this way the anticancer drug is specifically released into the tumor cells to exert its cytotoxic effects, while sparing normal cells. In conclusion, GnRH-R are expressed not only at the pituitary level but also in a wide range of tumor tissues; these receptors are at present under investigation as an effective molecular target for the development of novel therapeutic strategies.

The effect of injection and topical application of hCG and GnRH agonist to induce sperm-release in the roseate frog, Geocrinia rosea.

Reproductive technologies may assist amphibian conservation breeding programs (CBPs) to achieve propagation targets and genetic management goals. However, a trial-and-error approach to protocol refinement has led to few amphibian CBPs routinely employing reproductive technologies with predictable outcomes. Additionally, while injections can be safely administered to amphibians, perceived animal welfare risks, such as injury and disease transmission, warrant the development of alternative hormone administration protocols. The present study investigated the spermiation response of roseate frogs, Geocrinia rosea, administered various doses of human chorionic gonadotropin (hCG) and gonadotropin-releasing hormone agonist (GnRH-a) via subcutaneous injection. This study also quantified the spermiation response of frogs administered both hormones via topical application. Total sperm, sperm concentration and sperm viability were assessed over a 12-h period post hormone administration. Males released sperm in response to the injection of hCG (88-100% response; 5, 10 or 20IU), but all samples collected from males administered hCG topically (100, 100 + DMSO or 200IU hCG) were aspermic. In contrast, males consistently released sperm in response to both the injection (100% response; 1, 5 or 10 μg), or topical application (80-100% response; 50, 50 + DMSO or 100 μg) of GnRH-a. Overall, the administration of GnRH-a was more effective at inducing spermiation than hCG. Mean total sperm and sperm concentration were highest in response to the optimal topically applied dose of 100μg GnRH-a (mean total sperm = 2.44 × 103, sperm concentration = 1.48 × 105 sperm/ml). We provide novel evidence that topical application provides a viable alternative to injection for the administration of GnRH-a to induce spermiation in amphibians.

Effect of Timing of Gonadotropin-Releasing Hormone Agonist Administration for Ovarian Protection in Patients with Breast Cancer.

PurposeThis study was performed to investigate the effect of the interval between the start of gonadotropin-releasing hormone agonist (GnRHa) and the start of chemotherapy on ovarian protection in patients with breast cancer.MethodsThis was a prospective observational cohort study that included 136 patients with breast cancer below 40 years who received GnRHa during chemotherapy for fertility preservation. Plasma anti-Müllerian hormone (AMH) levels were measured before chemotherapy (baseline) and after chemotherapy. Subjects were divided into 3 groups according to the interval between the start of GnRHa and the start of chemotherapy for analysis: 1–6 days, 7–13 days, and ≥ 14 days. The ratio of the post-chemotherapy AMH value to the baseline AMH (pcAMH) at each time point were compared among the 3 groups. Ranked analysis of covariance was used for statistical analysis, adjusted for age, body mass index (BMI), and the existence of polycystic ovaries (PCOs). In addition, recovery of ovarian function (AMH ≥ 1 ng/mL) at 12 months was evaluated.ResultsThe median age of the patients was 32 years. There was no difference in the baseline AMH levels among the 3 groups (mean ± standard error: 5.0 ± 0.4 ng/mL [1–6 days], 5.3 ± 0.7 ng/mL [7–13 days], and 8.1 ± 1.3 ng/mL [≥ 14 days]; p = 0.250). The pcAMH at 3, 6, 12, 24, and 36 months were not significantly different among the 3 groups (p-values were 0.332, 0.732, 0.830, 0.148, and 0.393, respectively). In multivariate analysis, young age (p = 0.024), low BMI (p = 0.013), and the existence of PCO (p = 0.015) were predictors for AMH ≥ 1 ng/mL at 12 months.ConclusionThere was no difference in the ovarian protective effect according to the difference in the timing of administration of GnRHa.

Administration effects of single-dose GnRH agonist for luteal support in females undertaking IVF/ICSI cycles: A meta-analysis of randomized controlled trials.

The aim of the present meta-analysis was to evaluate the effects of the addition of single-dose gonadotropin-releasing hormone agonist (GnRHa) for luteal support on pregnancy outcomes in females partaking in in vitro fertilization or intracytoplasmic sperm injection cycles. In total, the studies were hand-searched from six electronic databases to compare the pregnancy outcomes between single-dose GnRHa administered as luteal phase support (GnRHa group) and regular luteal support (control group). In the GnRHa group, single-dose GnRH agonist were administered at 5/6 days after IVF/ICSI procedures. In the control group, single-dose GnRH agonist was not added during luteal phase support. Only randomized controlled trials were included. Sensitivity analysis was performed using Revman 5.3 software; the high heterogeneity identified in the present analysis was primarily caused by one study included. Following exclusion of this particular study, the meta-analysis results indicated significantly higher rates of ongoing pregnancy or live birth per transfer (P=0.002), clinical pregnancy per transfer (CPR; P=0.001) and multiple pregnancy per pregnancy (P=0.020) in the GnRHa group compared with those in the control group. Meta-analysis of a subgroup of trials with long-acting GnRH-a ovarian treatment protocols indicated that the rate of ongoing pregnancy or live birth (P=0.080), CPR (P=0.090) and multiple pregnancy per pregnancy (P=0.140) were not significantly different between the two groups. However, the results from trials that had used a multi-dose GnRH antagonist ovarian treatment protocol indicated a significantly higher ongoing pregnancy or live birth rate per transfer (P=0.010), CPR per transfer (P<0.0001) and multiple pregnancy rate per pregnancy (P=0.003) compared with those in the control group. The present results suggested that administration of single-dose GnRH agonist in the luteal phase may be an ideal choice for patients undergoing IVF/ICSI therapy.

Is gonadotropin-releasing hormone agonist usage really leading to thyroid dysfunction?

ObjectivesGonadotropin-releasing hormone agonist (GnRHa) could influence the levels of sex hormones and thyroid hormones. The aim of this study was to investigate the effect of GnRHa on thyroid function.Materials and methodsThe data of the patients were collected from the registrations of July 2014–October 2014. A total of 41 women who underwent one-time IVF cyclus were evaluated in this cross-sectional study. The patients were categorized into two groups according to the serum T3, T4, and TSH levels before and 2 weeks’ after the administration of GnRHa.ResultsMean basal TSH and mean TSH levels on hCG day were 1.98 ± 0.77 and 1.75 ± 0.70, respectively. The difference between the two groups was statistically significant (p < 0.05). GnRHa did not lead to statistically significant difference on serum-free T3 and T4 levels.ConclusionsIn conclusion, our results demonstrate that GnRHa led to a decrease on serum TSH level. Serum-free T3 and T4 levels were remained unchanged and this might be due to early measurement of the hormone levels (just 2 weeks later from GnRHa administration).

Recurrence of uterine adenomyosis after administration of gonadotropin-releasing hormone agonist and the efficacy of dienogest

This study elucidated the degree of adenomyosis recurrence following gonadotropin-releasing hormone agonist (GnRHa) discontinuation and dienogest efficiency for recurrent adenomyosis. This retrospective cohort study included 30 patients, divided into a group of patients whose progress was observed without providing additional therapy following GnRHa administration for six months (Group G) and a group of patients administered dienogest for six months following six months of GnRHa administration (Group D). Menorrhagia, dysmenorrhea, chronic pelvic pain, abdominal fullness, and uterine volume were recorded prior to treatment, six months after the start of therapy (6 M), and 12 months after the start of therapy (12 M). In Group G (n = 15), although all subjective symptoms disappeared at 6 M, nearly all symptoms recurred at 12 M. Uterine volume significantly decreased from 341.0 cm3 to 156.0 cm3 at 6 M (p = .001) and significantly increased again to 282.3 cm3 at 12 M (p = .003). In Group D (n = 15), all subjective symptoms disappeared at 6 M, and only abdominal fullness returned in a significant number of patients (5 of 5; p = .021) at 12 M. Uterine volume decreased significantly at 6 M (p = .003) and significantly increased again from 162.5 cm3 to 205.6 cm3 at 12 M (p = .006). Subjective symptoms, except for abdominal fullness, did not recur when dienogest was administered after GnRHa.

Effect of GnRHa on plasma levels of Fsh and Lh in the female greater amberjack Seriola dumerili.

The effects of gonadotropin-releasing hormone agonist (GnRHa) on plasma levels of follicle-stimulating hormone (Fsh) and luteinising hormone (Lh) are reported for female greater amberjack Seriola dumerili with post-vitellogenic ovarian oocytes. Five females were implanted with pellets containing GnRHa (600 μg kg-1 body weight), while five other females were injected with saline. All females implanted with GnRHa-containing pellets ovulated 36-42 h post-implantation. The GnRHa implants elevated Lh, but not Fsh plasma levels within 42 h of GnRHa administration.

1038P - The feasibility and efficacy of gonadotropin-releasing hormone agonists for prevention of chemotherapy-induced ovarian insufficiency in patient with malignant ovarian germ cell tumours

BackgroundTo assess the effects of a gonadotropin-releasing hormone agonists (GnRHa) administration in young patients with malignant ovarian germ cell tumour (MOGCT) during chemotherapy on the prevention of chemotherapy-induced ovarian insufficiency. MethodsThis multicenter, retrospective study was conducted at fifteen sites in Korea and enrolled 354 patients between January 1995 and January 2018. Among them 227 patients were included in this study according the inclusion criteria: 1) patients diagnosed as pathologically malignant germ cell tumours of the ovaries, 2) who have preserved the uterus and at least one ovary, 3) who received postoperative chemotherapy at least 3 cycles, 4) age at diagnosis, after menarche ∼ < 40 years old, 5) available clinical information on menstrual resumption. Patients were divided into two groups according to the use of GnRHa during chemotherapy (GnRHa group and non-GnRHa group) and compared the incidence of early menopause. ResultsThere was no difference in age, parity, menarche, stage, and type of operation (unilateral or bi-lateral adnexal surgery) among the two groups. The distribution of histology and types of chemotherapy drugs were different. After the end of chemotherapy, the resumption of menstruation was 100% in GnRHa group and 91% in non-GnRHa group (p=0.0132). The univariate analysis of the factors affecting menstrual resumption showed that the use of GnRHa during chemotherapy was statistically significant difference (OR, 0.00 (0∼0.69;95% CI, p=0.013). ConclusionsThe present findings provide evidence for the efficacy of temporary ovarian suppression with GnRHa during chemotherapy as an available option to reduce the likelihood of chemotherapy-induced ovarian insufficiency and potentially improve fertility in young patients with MOGCT. Legal entity responsible for the studyThe author. FundingCHA Bundang Medical Centre. DisclosureThe author has declared no conflicts of interest.

EP28.05: Uncomplicated pregnancy‐derived uterine arteriovenous malformations should be conservatively managed by ultrasound‐based triage and GnRHa administration

To report conservative management of post-miscarriage uterine arteriovenous malformations (AVM) diagnosed by 2- and 3-dimensional transvaginal sonography with colour or power Doppler assessment (2D-3D-TVS) and conservatively managed by gonadotropin-releasing hormone agonist (GnRHa) administration. Consecutive fertile patients with a recent history of first trimester miscarriage or abortion were considered. 2D-3D-TVS was performed by the GE Voluson E8 unit, using a wide-band 3-9 MHz transducer. Criteria for the sonographic diagnosis were presence of an irregular lobulated myometrial lesion with mixed echogenicity by 2D TVS imaging, on sagittal and/or transverse section of the uterus, adjacent to the uterine cavity with or without clearly visible products of conception, with abundant intralesional vascularisation (colour score 4), and high velocity blood flow within the vascular “web” with a peak systolic velocity (PSV) of > 20 cm/sec by colour or power Doppler imaging. In the absence of significant bleeding, a proper counseling and informed consent, a 3.75mg GnRH agonist was selectively administered. A sonographic follow-up was given within two months. Eight patients were enrolled. Median age was 33 years (IR 29-35). Median lesion diameter and volume were 25mm (IR 23-31) and 8cm3 (IR 6-14). Median PSV was 32 cm/sec (IR 29-38). In all patients the myometrial lesion spontaneously and uneventfully disappeared within the two months' follow-up period. Ultrasound based triage by 2D-3D-TVS with colour or power Doppler assessment should be considered the gold standard for diagnosis of AVM, being the simplest and most cost-effective diagnostic imaging modality. Conservative management of uncomplicated patients should be based on GnRHa and sonographic follow-up. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Fertility preservation in chemo-radiotherapy for rectal cancer: A combined approach

IntroductionColorectal cancer is a very common form of cancer worldwide, affecting an increasing number of young women. Standard treatment for locally advanced rectal cancer (LARC) can pose a threat to fertility in these patients. Case presentationWe present the case of a young woman affected by LARC who expressed a desire for child-bearing. The treatment she was proposed, according to guidelines, was neoadjuvant chemo-radiotherapy (CRT) followed by delayed surgery, carrying with it a high risk for amenorrhea. Counselling was performed before the initiation of treatment, with the aim of preserving fertility by the proposal of GnRH agonist administration, ovarian transposition and ovarian tissue cryopreservation, which the patient accepted. Treatment was then successfully completed. The patient presented regular menstrual period from before the surgery. DiscussionOvarian tissue is very sensitive to radiations. Transposition of the organ can prevent ovarian insufficiency by placing it outside the radiation field, while ovarian tissue cryopreservation and orthotopic transplantation offers the possibility to restore fertility in the case of organ failure. We performed both of the techniques. GnRH analogs administration allowed to diminish the risk of ovarian cytotoxicity. Radiation treatment plan was optimized in order to minimize the dose to organs at risk (ovary and vagina in particular); position of the uterus, which is quite radiosensitive too, was monitored with daily cone-beam CT (CBCT). ConclusionThe strategy proposed seemed safe and effective, resulting in radical treatment and persistence of regular menstrual period. Further studies are needed.

Evaluation of uterine receptivity after gonadotropin releasing hormone agonist administration as an oocyte maturation trigger: a rodent model

In natural cycle or minimal stimulation cycle IVF, buserelin acetate (buserelin), a gonadotropin-releasing hormone agonist, is often used as a maturation trigger; however, its effect on pregnancy outcomes remains unclear. Therefore, in the present study, we compared uterine receptivity in buserelin-administered mice with that in human chorionic gonadotropin (hCG)-administered mice during the peri-implantation period. Implantation, decidualisation, and term-pregnancy were impaired following hCG, but not buserelin administration. hCG stimulated the synthesis and secretion of progesterone and oestradiol, whereas ovarian steroidogenesis in the buserelin-treated group was comparable with that in the control group. Furthermore, similar to the observation in controls, the buserelin-treated group exhibited activation of progesterone receptor signalling and inhibition of oestrogen receptor signalling in the endometrial epithelium on the day of implantation. However, epithelial progesterone signalling was not detected, and a high expression of genes downstream to oestrogen was observed on day 4 following hCG administration. These results suggest that buserelin administration does not impact uterine receptivity as it did not affect ovarian steroidogenesis and endometrial steroid signalling. Therefore, buserelin is preferred as an oocyte maturation trigger to optimise uterine receptivity during treatments involving timed intercourse, intrauterine insemination, or fresh embryo transfer following in vitro fertilisation.