Effect Of Gonadotropin-releasing Hormone Agonist Research Articles

Long-term effects of GnRH agonist treatment on body mass index in girls with idiopathic central precocious puberty.

Introduction Studies evaluating effects of gonadotropin-releasing hormone agonist (GnRHa) on weight and body-mass-index (BMI) in girls with idiopathic central precocious puberty (iCPP) include short-term effects. The aim of this study is to investigate changes in BMI during and 2 years after completion of GnRHa to determine the factors that may impact BMI in girls with iCPP. Methods Medical files of 138 girls who completed GnRHa were evaluated. All patients had weight and height measurements at the beginning and end of treatment, and 111 patients had anthropometric measurements 2 years after the completion of treatment. Results In the beginning, 82 (59.4%) had normal weight (NW), 42 (30.4%) were overweight (OW), and 14 (10.2%) were obese (OB). Analysis of BMI-standard deviation score (SDS) in the whole group showed an overall increase during GnRHa treatment (0.92 ± 0.74 vs. 1.20 ± 0.51, p < 0.001). Changes in BMI-SDS (ΔBMI-SDS) during GnRHa differed between NW and OW/OB (0.45 ± 0.31 vs. 0.03 ± 0.20, p < 0.001). BMI-SDSs of both groups returned to baseline scores (or initial levels) 2 years after the completion of treatment. Two factors affecting ΔBMI-SDS in multiple linear regression analyses were baseline BMI and Δheight-SDS, both correlated negatively with ΔBMI-SDS. Conclusions The present study is one of the studies evaluating BMI change over a long period of time in girls with CPP. Although BMI-SDS increased during GnRHa in NW girls, it was reversible in follow-up after treatment. However, BMI-SDS did not change during and in follow-up in OW/OB girls. Conserving BMI-SDS in OW/OB girls may be related to the fact that weight management programs were recommended for these patients. Dietary recommendations should be provided for children with NW who undergo GnRHa, as is the case for OW patients.

Testicular expression of long non\u2013coding RNAs is affected by curative GnRHa treatment of cryptorchidism

BackgroundCryptorchidism is a frequent endocrinopathy in boys that has been associated with an increased risk of developing testicular cancer and infertility. The condition is curable by combined surgery and hormonal treatment during early pre-pubertal stages using gonadotropin releasing hormone agonist (GnRHa). However, whether the treatment also alters the expression of testicular long non-coding RNAs (lncRNAs) is unknown. To gain insight into the effect of GnRHa on testicular lncRNA levels, we re-analyzed an expression dataset generated from testicular biopsies obtained during orchidopexy for bilateral cryptorchidism.ResultsWe identified EGFR-AS1, Linc-ROR, LINC00221, LINC00261, LINC00282, LINC00293, LINC00303, LINC00898, LINC00994, LINC01121, LINC01553, and MTOR-AS1 as potentially relevant for the stimulation of cell proliferation mediated by GnRHa based on their direct or indirect association with rapidly dividing cells in normal and pathological tissues. Surgery alone failed to alter the expression of these transcripts.ConclusionGiven that lncRNAs can cooperate with chromatin-modifying enzymes to promote epigenetic regulation of genes, GnRHa treatment may act as a surrogate for mini-puberty by triggering the differentiation of Ad spermatogonia via lncRNA-mediated epigenetic effects. Our work provides additional molecular evidence that infertility and azoospermia in cryptorchidism, resulting from defective mini-puberty cannot be cured with successful orchidopexy alone.

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).

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.

Decreased Level of Neurotrophic Factor Neuritin 1 in Women with Ovarian Endometriosis after Receiving Gonadotropin-Releasing Hormone Agonist Treatment.

This study aimed to investigate the effect of gonadotropin-releasing hormone agonist (GnRHa) treatment on the expression of neuritin 1 (NRN1) in women with ovarian endometriosis. We collected tissues and serum from women with endometriosis treated with (n = 45) or without (n = 37) GnRHa. NRN1 mRNA and protein levels were measured using qPCR and Western blot. Immunolocalization of NRN1 in endometriotic tissues was examined using immunohistochemistry. In addition, a follow-up study was carried out to monitor the serum level of NRN1 in patients before and after GnRHa treatment. Both mRNA (p = 0.046) and protein (p = 0.0155) levels of NRN1 were significantly lower in endometriotic tissues from patients receiving GnRHa treatment compared to the untreated group. Both epithelial and stromal cells of endometriotic tissues from untreated women with endometriosis exhibited stronger staining of NRN1 but not in those who were treated with GnRHa. The follow-up study showed that the serum level of the NRN1 concentration decreased significantly from 1149 ± 192.3 to 379.2 ± 80.16 pg/mL after GnRHa treatment (p = 0.0098). The expression of NRN1 was significantly lower in women with ovarian endometriosis treated with GnRHa. These results suggest that NRN1 may be a biomarker response to the effect of GnRHa treatment for patients with ovarian endometriosis.

The impact of multiple-dose paclitaxel on fertility in mice and the protective effect of gonadotropin releasing hormone-agonist

Chemotherapeutic agents have numerous side effects. However, whether paclitaxel, the best-selling agent, causes premature ovarian failure is still controversial. In addition, most of articles only used single-dose paclitaxel, which was far from clinical dosage, to show the findings. Thus, further studies should be made on multiple doses. Besides, with the increase in incidence and the decrease in fatality of some cancers, the demand for ovarian protection is soaring. Gonadotropin releasing hormone agonists (GnRHa) are the most widely used agents for ovarian protection during chemotherapy. However, the available evidence is insufficient. And, the protective effect of GnRHa to ovaries from paclitaxel remains unclear. Our study is going to demonstrate the phenomena and duration of the gonadotoxicity caused by multiple-dose paclitaxel and to investigate the protective effect of GnRHa meanwhile via mimicking the clinical dosages and intervals in NCCN guidelines. Three subsequent doses of 30 mg/kg paclitaxel(1 dose per 3 days) or an equal volume of vehicle was given intraperitoneally to 7-week-old female ICR mice. These mice were given 1 mg/kg GnRHa(every day) or normal saline for one estrous cycle before, during and another estrous cycle after chemotherapy. On the 1st, 6th, 11th or 16th day after the multiple-dose paclitaxel, the mice were managed in several ways: follicle counting (n=5/group/time point), acquisition of oocytes (n=5/group/time point) and immunofluorescence. 1.Seven-week-old female ICR mice 2. GnRHa (triptorelin acetate, Ferring AG, Switzerland),paclitaxel (Hospira Australia Pte Ltd) 3.Histology and follicle count 4. Oocyte collection 5. Immunofluorescence 6.Statistical analysis. The follicle counting showed that paclitaxel only destroyed antral follicles for 2 estrous cycles after chemotherapies and induced increasing atretic follicles without affecting follicles in other stages. Add GnRHa to paclitaxel significantly reduced the amount of atretic follicles(30.60±5.00 versus 63.80±4.00, P<0.05). Moreover, the ovarian stimulation was also performed to determine the duration of the gonadotoxicity after multiple-dose paclitaxel. The acquisition of MⅡ oocytes in paclitaxel-only group was extremely less on the 1st and 6th day after the last dose of the treatment(D1: 1.00±0.00 versus 30.40±5.27, P<0.01; D6: 17.20±4.25 versus 31.33±4.67, P<0.05). Compare to the control, mice, with the protection of GnRHa, ovulated even more MⅡ oocytes on the 6th day after chemotherapies(46.80±3.44 versus 31.33±4.67, P<0.05). And up to 2 estrous cycles after the last dose, the quantity of MⅡ oocytes in all groups showed no statistical difference. Meanwhile, the morphology of oocytes was observed by immunofluorescence. These results indicated that paclitaxel mainly impacted antral follicles and the gonadotoxicity lasted no more than 2 estrous cycles of mice. The protective effect of GnRHa on ovaries was significant. This study provides a laboratory evidence for the impact of paclitaxel and the effectiveness of GnRHa in clinical practice.

Effect of Gonadotrophin-Releasing Hormone Agonist Addition for Luteal Support on Pregnancy Outcome in vitro Fertilization/Intracytoplasmic Sperm Injection Cycles: A Meta-Analysis Based on Randomized Controlled Trials

Purpose: The meta-analysis aimed to evaluate the effect of gonadotrophin-releasing hormone agonist (GnRH-a) addition for luteal support on pregnancy outcome in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Methods: Meta-analysis. Results: A total of 3,584 cycles were identified from 13 randomized controlled trials. The cumulative analysis showed that GnRH-a addition for luteal supports significantly improved live birth rate (relative risk [RR] = 1.52; 95% CI 1.20–1.94; p = 0.0006), the clinical pregnancy rate (RR 1.21; 95% CI 1.11–1.33; p < 0.0001), ongoing pregnancy rate (RR 1.18; 95% CI 1.06–1.32; p = 0.004), pregnancy rate (RR 1.36; 95% CI 1.01–1.82; p = 0.04), implantation rate (RR 1.44; 95% CI 1.17–1.77; p = 0.0007), and multiple pregnancy rate (RR 1.40; 95% CI 1.04–1.88; p = 0.03) in comparison with control, but not for the incidence of ovarian hyperstimulation syndrome (RR 0.96; 95% CI 0.32–2.89; p = 0.94). We also found that GnRH-a addition for luteal support had a tendency to decrease the abortion rate (RR 0.72; 95% CI 0.56–0.93; p = 0.01). Conclusions: Overall, the current meta-analysis showed a substantial efficacy of GnRH-a addition for luteal support on pregnancy outcomes in women undergoing IVF/ICSI and support the use of GnRH-a in luteal phase to improve the success of IVF/ICSI.

Psychological effects of gonadotropin-releasing hormone agonist treatment in girls with central precocious puberty.

Objective This study was done to evaluate the emotional and behavioral status of precocious puberty patients and analyze the effect of gonadotropin-releasing hormone agonist (GnRHa) treatment. Methods Sixty-six female precocious puberty patients were enrolled prospectively for the study at Kangdong Sacred Heart Hospital of Hallym University Medical Center from September 2011 to December 2012 and self-administered questionnaire was completed during the GnRHa treatment initiation period and after 12 months from the first injection. The patients were evaluated using the Korean version of Child Behavior Checklist (K-CBCL) and Children's Depression Inventory (CDI). Results A total of 30.3% (n = 20) of the patients scored within the clinical range for one or more scales of K-CBCL at the initiation of GnRHa treatment, but only 10.6% (seven patients) were within the clinical range after 1 year of treatment. Average CDI scores of the patients decreased from baseline 6.5 ± 6.0 to 4.9 ± 4.7 after GnRHa therapy. Conclusions This study shows that both K-CBCL and CDI scores improved from baseline score ranges after 1 year of GnRHa treatment in female central precocious puberty patients while significant psychological problems of clinical range amongst them were not noted.

Anti-Müllerian hormone as a new marker of the ovarian reserve function preservation by goserelin during (neo)adjuvant chemotherapy for young breast cancer patients

To observe the dynamic change of anti-Müllerian hormone (AMH) in 1 year after chemotherapy which is the best biochemical marker of ovarian reserve in reproductive medicine setting and to evaluate the effect of gonadotropin-releasing hormone agonist (GnRHa)goserelin to prevent ovarian reserve function during (neo)adjuvant chemotherapy for young breast cancer patients. Between December 2015 and June 2017, 101 breast cancer patients of age ≤ 45 years with stages I to III had been enrolled. The patients were assigned without interference to receive either (neo) adjuvant chemotherapy with goserelin (goserelin group) or without goserelin (chemotherapy group) as their own selection. AMH and menstrual status were evaluated before, during and 0.5 year, 1 year after chemotherapy. Primary end point was the incidence of low AMH value (<0.4 μg/L) at the end of 1 year. Secondary end point was the incidence of amenorrhea (the absence of menses in the preceding 12 months after assignment). In the study, 51 patients chose to join the chemotherapy group, while the other 50 patients selected goserelin to preserve their ovarian reserve function. More unmarried or childless, hormone receptors negative,receiving breast conservation therapy patients with earlier stage selected goserelin before chemotherapy. The incidence of low AMH value was significantly higher in chemotherapy group than in goserelin group (74.5% vs. 38.0%, P<0.001) in 1 year after chemotherapy. The incidence of amenorrhea was consistent with AMH (56.9% vs. 24.0%, P=0.001). And more patients' menstruation (78.9% vs. 54.5%) and AMH value (71.0% vs. 53.8%) recovered in goserelin group within 6 months after chemotherapy. In subgroup analysis, AMH and menstruation seemingly recovered more in goserelin group independent of age, chemotherapy regimen and use of tamoxifen. Especially, AMH value of 36.4% (8/22) patients in chemotherapy group and 18.4% (7/38) patients in goserelin group still maintained low level (<0.4 μg /L) although their menstruation had recovered 1 year after chemotherapy. In addition, 41 patients (20 patients in chemotherapy group, 21 patients in goserelin group) could be evaluated for the dynamic change of AMH and menstrual status during chemotherapy. The mean level of AMH in chemotherapy group declined rapidly to very low level before the 3rd cycle, while 70% of the patients kept presence of menstruation. At the same time, the mean level of AMH in goserelin group was still above 0.4 μg /L, but all of the patients had menopause. Our study has offered evidence that Goserelin with chemotherapy could protect against ovarian reserve failure for young breast cancer patients, now that more patients' AMH value recovered earlier who had selected co-treatment. AMH may be a more precise marker than menstrual status to clinically evaluate ovarian reserve function pre-, during and post- chemotherapy.

Effect of GnRH agonist and letrozole treatment in women with recurrent implantation failure

To compare the influence of dual suppression with the use of GnRH agonist plus aromatase inhibitor compared with suppression with the use of GnRH agonist alone or no suppression at all in patients with idiopathic recurrent implantation failure (RIF). Retrospective cohort study. University-affiliated reproductive center. A total of 523 infertile women who failed two blastocyst transfers underwent a third frozen blastocyst transfer. Women with known endometriosis were excluded. A total of 204 subjects were not pretreated, 143 received 2months of GnRH agonist (3.75mg intramuscular leuprolide acetate monthly) only, and 176 received GnRH agonist and aromatase inhibitor (5mg oral letrozole daily for 60days). Demographic and stimulation information was collected and cycle outcomes reported. Clinical pregnancy rates. Age, antral follicle count, basal FSH levels, duration of infertility, previous pregnancies, and full-term deliveries were similar (P>.05). Clinical pregnancy rates were higher among women who received GnRH agonist plus letrozole compared with women who received GnRH agonist only or women without pretreatment (63%, 42%, and 40%, respectively; P<.0001). Live birth rates were higher among women who received GnRH agonist plus letrozole compared with the other groups (56%, 36%, and 34%; P<.0001). No differences in pregnancy outcomes were noted between patients who did not receive pretreatment and those in the GnRH agonist only group. In patients with RIF, treatment with a GnRH agonist plus letrozole may improve live birth rates in subsequent cycles. We hypothesize that this improvement is due to alterations in the endometrium receptivity or treatment of undiagnosed endometriosis.

Prolonged pituitary down-regulation with full-dose of gonadotropin-releasing hormone agonist in different menstrual cycles: a retrospective cohort study.

BackgroundThe efficiency of prolonged down-regulation caused by a full-dose of gonadotropin-releasing hormone agonist (GnRH-a) injected during different menstrual phases has not yet been researched. Our goal was to evaluate the effects of GnRH-a, which was used in different phases of the menstrual cycle in patients undergoing in vitro fertilization and embryo transfer.MethodsThis was a retrospective cohort study. A total of 320 patients received a prolonged pituitary down-regulated full-dose (3.75 mg) of triptorelin in the early follicular phase, and 160 patients received the same full-dose of triptorelin during the mid-luteal phase. Clinical and laboratory outcomes were compared between the two groups.ResultsThe basic characteristics of the two groups were comparable. The mean number of retrieved oocytes, fertilized oocytes, cleavage oocytes and good quality embryos were comparable between the two groups. Although there was a higher antral follicle count, cyst formation rate, fertilization rate and cleavage rate in the follicular phase group, no statistically significant effects were seen on implantation rate (41.15% vs. 45.91%), clinical pregnancy rate (60.38% vs. 61.36%), ongoing pregnancy rate (57.74% vs. 57.58%), live birth rate (56.23% vs. 57.58%) or early abortion rate (2.64% vs. 3.79%) per fresh transfer cycle. Moreover, severe ovarian hyperstimulation syndrome rates at the early stage (1.89% vs. 2.27%) were low in both groups.ConclusionsProlonged pituitary down-regulation achieved by utilizing a full-dose of GnRH-a administrated in either phase of the menstrual cycle can have a positive effect on ongoing pregnancy rate and live-birth rate per fresh embryo transfer cycle. Ovarian cyst formation rate was higher in the follicular phase group, but this did not have any adverse impact on clinical results.

Protective effect of gonadotropin-releasing hormone agonist against chemotherapy-induced ovarian dysfunction: A meta-analysis.

The protective effects of gonadotropin-releasing hormone agonist (GnRHa) against ovarian chemotherapy induced-toxicity have not completely been demonstrated and the impact of chemotherapy on ovarian dysfunction remains unclear. The present meta-analysis aimed to evaluate the efficiency of GnRHa and to determine whether GnRHa could influence the long-term survival rate of patients with cancer. A total of 12 clinical randomized controlled trials were included, consisting of 1,413 patients who were divided into the GnRHa group (n=705) and the control group (n=708). The meta-analysis revealed that GnRHa may significantly improve the menstrual function recovery rate in patients who received chemotherapy [RR=1.29, 95% confidence interval (CI)=1.09–1.54, P=0.004] and reduce the rate of premature ovarian failure (RR=0.47, 95% CI=0.31–0.71, P=0.0004). However, it had no effect on the pregnancy rate (RR=1.40, 95% CI=0.98–1.98, P=0.06), on the rate of disease-free survival and overall survival of patients (disease-free survival rate: RR=1.04, 95% CI=0.95–1.13, P=0.40; overall survival rate: RR=1.02, 95% CI=0.90–1.16, P=0.72). In conclusion, GnRHa may reduce chemotherapy-induced ovarian dysfunction without compromising or influencing the therapeutic effects of chemotherapy.

SUN-267 Relationship between Height Velocity and Change of Serum Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor Binding Protein-3 Concentrations during Gonadotropin-Releasing Hormone Agonist Treatment in Korean Girls with Idiopathic Central Precocious Puberty

Purpose : This study aims to investigate the effect of gonadotropin-releasing hormone agonist (GnRHa) on the growth velocity during treatment in Korean girls with idiopathic central precocious puberty (ICPP). Methods : Data was collected from 97 girls, diagnosed under 9 year of age and treated by GnRHa for at least 1 year between 2014 and 2015. Their body height, weight, ∆ Height standard deviation score (SDS), serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) concentrations and bone age were measured at the start and after a year of GnRHa treatment. Possible correlations between the variables were calculated. Results : During the treatment, height SDS, IGF-1 SDS, IGFBP-3 SDS and IGF-1/IGFBP-3 ratio significantly decreased. There were significant correlations between serum IGF-1 level and ∆ Height SDS (r=0.405, p=0.000), and between serum IGFBP-3 level and ∆ Height SDS (r=0.228, p=0.025). C allele had significant correlation with IGFBP-3 level (p=0.004) but had no significant correlation with ∆ Height SDS (p=0.947). Conclusions : The results suggest that the height velocity during GnRHa treatment may be related to serum IGF-1 and IGFBP-3 concentration thus GnRHa may affect GH-IGF-1 axis.

Serum Anti-Müllerian Hormone Is Significantly Altered by Downregulation With Daily Gonadotropin-Releasing Hormone Agonist: A Prospective Cohort Study.

Research Question: What is the effect of gonadotropin-releasing hormone (GnRH)-agonist treatment on serum anti-Müllerian hormone (AMH)?Design: This prospective cohort study conducted in a tertiary university hospital comprised patients (n = 52) who self-administered daily triptorelin (0.1 mg/0.1 mL) subcutaneously for 14 days from menstrual cycle day 21 ± 3, between July 2015 and March 2016. Enrolled women were 18–43 years old, considered normal ovarian responders, with a planned GnRH agonist controlled ovarian stimulation protocol. The primary endpoint was to evaluate the effect of GnRH agonist on serum AMH levels after 7 and 14 days of treatment.Results: Under GnRH agonist treatment, serum AMH was significantly decreased vs. baseline on day 7 (mean change from baseline: −0.265 ng/mL; 95% confidence interval [CI], −0.395 to −0.135 ng/mL; p < 0.001). On day 14, serum AMH was significantly increased (mean change from baseline: 0.289 ng/mL; 95% CI, 0.140–0.439 ng/mL; p < 0.001). Although the median change in AMH from baseline was only −14.9% on day 7 and +17.4% on day 14, from day 7 to 14 AMH significantly increased by 0.55 ng/mL (43.8%; p < 0.001), which is of paramount clinical importance. A linear, mixed-effect model demonstrated that GnRH agonist treatment for 7 and 14 days had a highly significant effect on serum AMH concentration after adjustment for confounding factors (age, body mass index, baseline antral follicle count, and visit). AMH assay precision was excellent (four aliquots/sample); coefficient of variation was 1.2–1.4%.Conclusions: GnRH agonist treatment had a clinically significant effect on serum AMH, dependent on treatment duration. The clear V-shaped response of AMH level to daily GnRH agonist treatment has important clinical implications for assessing ovarian reserve and predicting ovarian response, thus AMH measurements under GnRH agonist downregulation should be interpreted with great caution.

GnRHa for Ovarian Protection and the Association between AMH and Ovarian Function during Adjuvant Chemotherapy for Breast Cancer.

Background: Chemotherapy impairs ovarian function in premenopausal breast cancer patients. Many breast cancer patients experience menopause earlier and therefore lose their reproductive abilities. The protective effect of gonadotropin-releasing hormone agonist (GnRha) upon the ovary is clearly apparent for hormone receptor (HR) negative patients, although the available data is not consistent for the patient body as a whole when considered regardless of HR status. It is also unknown whether levels of Anti-Mullerian Hormone (AMH) can reflect the influence of chemotherapy upon the ovary.Methods: We randomly assigned 98 premenopausal breast cancer patients regardless HR-positive or -negative to receive either standard chemotherapy with GnRHa (GnRHa group) or standard chemotherapy without GnRHa (control group). Our primary end point was ovarian failure rate (OVF) at 1 year. In addition, we observed the change of AMH level during chemotherapy and the association between AMH and OVF.Results: OVF was significantly lower (44.7%) in the GnRHa group than in the control group (80.6%; P=0.002). Median AMH levels were significantly higher before chemotherapy when compared to after 1/2cycles of chemotherapy, both in the GnRHa group (1.86ng/ml vs 0.12ng/ml; P=0.000) and in the control group (1.57ng/ml vs 0.10ng/ml; P=0.000). OVF was 91.3% in the AMH baseline level <1.1ng/ml group and 63.5% in the AMH baseline level >1.1ng/ml group (P=0.013).Conclusion: Data showed that GnRHa may have a protective effect on young breast cancer patients regardless of HR during chemotherapy. AMH could reflect changes of OVF during chemotherapy and predict OVF after chemotherapy.

The effect of GnRH agonists on angiogenesis and its implications for the myocardium in patients with cardiac risk

Gonadotropin-releasing hormone agonists were described as anti-angiogenic factors in tumors. Simultaneously they were associated with increased cardiovascular risk in patients treated for prostate cancer, especially in those with preexisting cardiac disease. Studies aiming to elucidate the mechanisms by which androgen deprivation therapy causes cardiovascular effects are rare. We believe that gonadotropin-releasing hormone agonists can impair myocardial angiogenesis. That, in patients with myocardial disease can deepen hypoxia, significantly worsen the condition of the myocardium, and therefore increase the risk of cardiac failure. Careful assessment of the myocardial status and consequent timing and typing of therapy can minimalize the adverse effects. Ideally through close cooperation between cardiologists and oncologists (Fig. 1, Ref. 25). Keywords: angiogenesis, cardiovascular risk, follicle stimulating hormone, GnRH agonist, testosterone.

Effect of gonadotropin-releasing hormone agonist used before surgery on natural pregnancy rates in patients with ovarian endometriomas

Objective: To evaluate the impact of gonadotropin-releasing hormone agonist (GnRH-a) used before surgery on natural pregnancy rates in patients with ovarian endometriomas. Methods: In this retrospective study, 57 patients with ovarian endometriomas who had a consecutive laparoscopic surgery between June, 2010 to September, 2015 in Peking Union Medical College Hospital were included. Those patients were divided into preoperative GnRH-a treatment group (n=31) and non-GnRH-a treatment group (n=26) . There were no differences in patients' characteristics between the two groups. All of them had a desire for natural pregnancy postoperatively. GnRH-a was no longer used after surgery. After the surgical procedure, the patients were observed over a period of 12 months, during which the frequency of natural pregnancy was assessed. The two groups were compared in terms of natural pregnancy rates. Results: Totally 33 patients had natural pregnancy after surgery. The univariate analysis showed that the pregnancy rates of age, r-AFS stage, infertility, preoperative use of GnRH-a, tumor size, tumor side, deep infiltrating endometriosis and adenomyosis did not have statistically significant differences (all P>0.05) . The two classified logistic regression showed that OR for preoperative use of GnRH-a was 0.250 (95%CI: 0.064-0.978) with a statistical difference (P=0.046) . Conclusion: The use of GnRH-a preoperatively may have a negative effect on natural pregnancy rates of patients after surgery with ovarian endometriomas.

Effect of GnRHa on Th17/Treg cells in peripheral blood of patients with unexplained repeated implantation failure.

To investigate the effect and possible mechanism of downregulation of gonadotropin-releasing hormone agonist (GnRHa) on Th17/Treg (regulatory T cell) cells in peripheral blood of patients with unexplained repeated implantation failure (RIF). Fifty-two patients who had RIF (≥ 3 consecutive transfers of ≥ 4 high-grade embryos in women under the age of 40 (excluding 40)) of frozen-thawed embryos were studied. Twenty-nine cases receiving simple hormone replacement therapy (HRT) were defined as transfer group, and the remaining 23 cases with HRT combined with GnRHa downregulation were defined as GnRHa downregulation group. In addition, 30 cases of the normal early pregnancy group were selected as control group. Before HRT, the number of Th17 and Treg cells in CD4+ lymphocytes was increased and decreased, respectively, with the ratio of Th17/Treg cells increased in HRT group compared with the control group (p < 0.05). On the day of progesterone conversion, compared with the HRT group, the percentage of Th17 and Treg cells was decreased and increased, respectively, with the ratio of Th17/Treg cells decreased significantly in GnRHa downregulation group (p < 0.05). The estrogen E2 levels of the GnRHa downregulation group were slightly higher than those of the HRT group, with no significant difference between the two groups (p > 0.05). Further, there was no significant difference in the levels of chorionic gonadotropin at the 14th day and the 21st day after transplantation between HRT group and GnRHa downregulation group (p > 0.05). There were an increase and a decrease in the number of Th17 and Treg cells, respectively, with Th17/Treg cells imbalanced in unexplained RIF. GnRHa downregulation may play a direct immunomodulatory role in disrupting the imbalance and then improve the endometrial receptivity. These effects did not depend on the E2 levels in peripheral blood, nor affect early embryonic development.

The clinical effects of gonadotropin-releasing hormone agonists for the treatment of children patients with central precocious puberty.

We explored the clinical effect of gonadotropin-releasing hormone agonists for the treatment of children patients with central precocious puberty. From March 2012 to October 2015, 100 cases of children patients with central precocious puberty were enrolled in this study. Intramuscular injection of acetic acid triptorelin (50 to 100 pLg/kg) was made once every 4 weeks, and the treatment lasted for 4 months. Patients' bone age/height differentials (DBA/DCA), bone age (BA), growth velocity (GV) and predicted adult height (PAH) were determined before and after treatment (after 6, 12, 24, 36 months). Differences before and after treatment were analyzed. DBA/DCA, BA and PAH values 6, 12, 24, 36 months after treatment were significantly different compared with those before treatment. Sexual development symptoms in children patients were significantly improved 4 months after treatment (p<0.05). All patients completed the treatment, without any adverse drug reaction or severe complication. After one course of treatment (4 months), patients' uterus and ovarian volumes shrank, FSH level peaked, and LH level was reduced, compared to those before treatment. Acetate acid triptorelin is safe and reliable for treating central precocious puberty. We achieved the excellent clinical curative effect and were able to delay the growth rate in children patients. The predicted height and final height were improved.

Differential effects of depot formulations of GnRH agonist leuprorelin and antagonist degarelix on the seminiferous epithelium of the rat testis.

Despite their pharmacologically opposite actions, long-acting depot formulations of both GnRH agonists and antagonists have been clinically applied for treatment of androgen-sensitive prostate cancer. Sustained treatment with GnRH analogues commonly suppresses both the synthesis and release of gonadotropins, leading to depletion of testicular testosterone. To clarify the underlying differences in the effects of GnRH agonists and antagonists on spermatogenesis, we compared histological changes in the seminiferous epithelium after administration of depot formulations of GnRH agonist leuprorelin and antagonist degarelix to male rats. Testicular weight had markedly declined by 28 days after administration of both GnRH analogues, although the testicular weight was decreased more promptly by leuprorelin compared with degarelix. Shortly after administration, massive exfoliation of premature spermatids and anomalous multinucleated giant cells was observed in seminiferous tubules of leuprorelin-treated rats, probably via the initial hyperstimulatory effects on the hypothalamic-pituitary-testicular axis, whereas no discernible changes were found in those of degarelix-treated rats. Long term treatment with both types of GnRH analogues similarly induced a marked reduction in the height of the epithelium and deformation of apical cytoplasm in Sertoli cells, resulting in premature detachment of spermatids from the epithelium. Lipid droplets had accumulated progressively in Sertoli cells, especially in those of degarelix-treated rats. These findings clearly demonstrate the differences in the effects of GnRH agonists and antagonists on the spermatogenic process. This study suggests that an appropriate choice of GnRH analogues is necessary to minimize their adverse effects on spermatogenesis when reproductive functions should be preserved in patients.