Received Gonadotropin-releasing Hormone Agonists Research Articles

Comparison of ultra-long gonadotropin releasing hormone agonist versus standard downregulation in women with adenomyosis undergoing frozen-thawed embryo transfer: a randomized clinical trial

BackgroundAdenomyosis can lead to infertility and failure of in vitro fertilization. Limited evidence suggests that the use of long-term treatment with gonadotropin-releasing hormone (GnRH) agonists followed by frozen-thawed embryo transfer (FET) may be the preferred approach for women with adenomyosis.ObjectiveThe aim of this randomized controlled trial is to compare the efficacy of an ultra-long GnRH agonist with standard downregulation in women with adenomyosis undergoing FET.Materials and methodsThis randomized controlled trial enrolled 72 women with adenomyosis diagnosed by sonographic criteria who underwent FET cycles at the Avicenna Infertility Center. These women were randomly assigned to two equal groups: one received GnRH agonist treatment for three months before the FET cycle and the other served as the standard downregulation group. Results were reported as chemical and clinical pregnancy rates.ResultsThe two groups were similar in age, body mass index, anti-Müllerian hormone levels, number of previous pregnancies and miscarriages, presence of uterine myomas, and endometriosis. However, the total dose of estradiol used until embryo transfer was significantly higher in the ultra-long GnRH agonist group than in the standard group (96.14 mg vs. 80.52 mg, p-value = 0.004). Nevertheless, chemical and clinical pregnancy rates did not differ significantly between the two groups.ConclusionsUltra-long GnRH agonist downregulation did not improve the chemical and clinical pregnancy rate in the FET cycle in women with adenomyosis compared with standard GnRH agonist downregulation in the other words, ultra-long GnRH agonist downregulation is not superior to standard protocol. In women with adenomyosis (without history of endometriosis), downregulation of standard GnRH agonists prior to frozen-thawed embryo transfer may be the preferred embryo transfer protocol to gain higher clinical/chemical pregnancy rate.Trial registrationClinical trial registry: IRCT20160717028967N9, available at: https://irct.behdasht.gov.ir/trial/36103.

Incidence and severity of ovarian hyperstimulation syndrome (OHSS) in high responders after gonadotropin-releasing hormone (GnRH) agonist trigger in “freeze-all” approach

Objective To determine the incidence and severity of ovarian hyperstimulation syndrome (OHSS) in high responders (25–35 follicles with a diameter of ≥12 mm on day of triggering) who received a gonadotropin-releasing hormone (GnRH) agonist to trigger final follicular maturation. Methods We used individual data from women who participated in four different clinical trials and were high responders to ovarian stimulation in a GnRH antagonist protocol in this retrospective combined analysis. All women were evaluated for signs and symptoms of OHSS using identical criteria based on Golan’s system (1989). Results High responders (n = 77) were of different ethnicities. There were no differences in baseline characteristics between women with or without signs and symptoms of OHSS. Mean ± standard deviation baseline data were: age, 32.3 ± 3.5 years; anti-Müllerian hormone, 42.4 ± 20.7 pmol/L; antral follicle count, 21.5 ± 9.2. Before triggering, duration of stimulation was 9.5 ± 1.6 days and the mean number of follicles with a diameter of ≥12 mm and ≥17 mm was 26.5 ± 4.4 and 8.8 ± 4.7, respectively. Mean serum estradiol (17,159 pmol/l) and progesterone (5.1 nmol/l) levels were high at 36 h after triggering. Overall, 17/77 high responders (22%) developed signs and symptoms of mild OHSS which lasted 6–21 days. The most frequently prescribed medication was cabergoline to prevent worsening of OHSS. No severe OHSS occurred and no OHSS cases were reported as serious adverse events. Conclusions High responders receiving GnRH agonist for triggering should be informed that they may experience signs and symptoms of mild OHSS.

Gonadotropin-releasing hormone agonist treatment and ischemic heart disease among female patients with breast cancer: A cohort study.

The risk of ischemic heart disease (IHD) due to the impact of gonadotropin-releasing hormone (GnRH) agonists among female patients with breast cancer remains a controversy. Information from the Registry for Catastrophic Illness, the National Health Insurance Research Database (NHIRD), and the Death Registry Database in Taiwan were analyzed. Female patients with breast cancer were selected from the Registry for Catastrophic Illness from January 1, 2000, to December 31, 2018. All the breast cancer patients were followed until new-onset IHD diagnosis, death, or December 31, 2018. A Kaplan-Meier survival curve was drawn to show the difference between patients treated with and without GnRH agonists. The Cox regression analysis was used to investigate the effects of GnRH agonists and the incidence of IHD. A total of 172,850 female patients with breast cancer were recognized with a mean age of 52.6 years. Among them, 6071(3.5%) had received GnRH agonist therapy. Kaplan-Meier survival curves showed a significant difference between patients with and without GnRH therapy (log-rank p < 0.0001). Patients who received GnRH therapy had a significantly decreased risk of developing IHD than those without GnRH therapy (HR=0.18; 95% CI=0.14-0.23). After adjusting for age, treatment, and comorbidity, patients who received GnRH therapy still had a significantly lower risk of developing IHD (AHR=0.5, 95% CI=0.39-0.64). The study showed that the use of GnRH agonists for breast cancer treatment was significantly associated with a reduced risk of IHD. Further research is required to investigate the possible protective effect of GnRH on IHD.

The Effect of Stimulation Protocols (GnRH Agonist vs. Antagonist) on the Activity of mTOR and Hippo Pathways of Ovarian Granulosa Cells and Its Potential Correlation with the Outcomes of In Vitro Fertilization: A Hypothesis.

Controlled ovarian hyperstimulation (COH) is essential for the success of in vitro fertilization (IVF). Evidence showing the comparison of different COH protocols remains predominantly of low certainty and derives from unspecified infertile and highly heterogeneous populations. Thus, personalized approaches to examine the response of patients to the various COH protocols need to be investigated. Data from in vitro and animal studies have identified the mechanistic target of rapamycin (mTOR) and Hippo signaling pathways play a key role in follicular homeostasis and oocyte quality. To be specific, current data indicate the controlled activation of mTOR and the controlled inhibition of the Hippo pathway within the ovarian granulosa cells (GC). Both are reported to lead to a nurturing follicular microenvironment, increase oocyte quality, and potentially improve reproductive outcomes. As intracellular markers, phosphorylated/unphosphorylated levels of the pathways’ main downstream mediators could be included among the candidate “personalized” predictors of patients’ response to COH protocols and final IVF outcomes. Based on these hypotheses, we make a preliminary attempt to investigate their validity: We propose a prospective cohort study to compare the levels of certain phosphorylated/unphosphorylated components of the investigated pathways (mTOR, ribosomal protein S6 kinase beta-1 (p70S6K-1), yes-associated protein-1 (YAP-1), and transcriptional coactivator with PDZ-binding motif (TAZ)) within the follicular fluid-isolated GC between women undergoing gonadotropin-releasing hormone (GnRH) antagonist/“short” protocols and those receiving GnRH agonist/“long 21” protocols. A case-control design comparing these levels between women achieving pregnancy and those who did not is further planned. Additional analyses addressing the population’s expected heterogeneity are planned after the completion of the pilot phase, during which 100 participants undergoing IVF are intended to be recruited. At this stage, these hypotheses are solely based on in vitro/animal data, and thus, similar studies on humans in this respect are necessary for the investigation of their potential validity.

A randomized Clinical Trial comparing embryo quality and clinical pregnancy rate in PCOS patients underwent controlled ovarian stimulation using antagonist protocol with freeze all strategy and triggered for final oocyte maturation by gonadotropin agonist versus human chorionic gonadotropin in IVF cycles

Background: The use of Gonadotropin-releasing hormone (GnRH) antagonist protocol rather than the long agonist protocol showed a marked reduction in the incidence of OHSS Aim: To compare the effect of triggering oocytes by agonist versus HCG on reduction of risk of OHSS, embryo quality and clinical pregnancy rate. Patients and methods: A randomized Clinical Trial was conducted at IVF unit in Cairo University Obstetric and Gynecologic hospital. The patients were divided into two groups, the 1st group received GnRH agonist trigger, the 2nd group received hCG trigger; all embryos were frozen at day 5 and frozen embryos were transferred the next cycle. Results: There was an obvious reduction in the risk of OHSS in the GnRH agonist triggered group than in the HCG triggered group but with no statistically significant difference. In the current study, there was no statistically significant difference between the HCG triggered group in comparison to the GnRH agonist triggered group regarding chemical and clinical pregnancy rates. Conclusion: The use of GnRH triggering for women with PCOS undergoing ICSI cycle with antagonist protocol with freeze all and transfer of frozen embryos in a later cycle has a lower risk of OHSS than using HCG triggering method.

Effects of multiple doses of gonadotropin-releasing hormone agonist on the luteal-phase support in assisted reproductive cycles: A clinical trial study.

BackgroundThe effect of adding gonadotropin-releasing hormone (GnRH) agonist on the luteal phase support in assisted reproductive technique (ART) cycles is controversial.ObjectiveTo determine the effects of adding multiple doses of GnRH agonist to the routine luteal phase support on ART cycle outcomes.Materials and MethodsThis clinical trial study included 200 participants who underwent the antagonist protocol at the Research and Clinical Center for Infertility, Yazd, Iran, between January and March 2020. Of the 200, 168 cases who met the inclusion criteria were equally divided into two groups – the case and the control groups. Both groups received progesterone in the luteal phase, following which the case group received GnRH agonist subcutaneously (0/1 mg triptorelin) zero, three, and six days after the fresh embryo transfer, while the control group did not receive anything. Finally, chemical and clinical pregnancy rates, number of mature oocytes, fertilization rate, total dose of gonadotropin, and the estradiol level were determined.ResultsThe baseline characteristics were similar in both groups. No significant difference was observed between embryo transfer cycles. Clinical results showed that differences between the fertilization rate, chemical and clinical pregnancies were not significant.Conclusion The results showed that receiving multiple doses of GnRH agonist in the luteal phase of ART cycles neither improves embryo implantation nor the pregnancy rates; therefore, further studies are required.

Type of Androgen Deprivation Therapy and Risk of Dementia Among Patients With Prostate Cancer in Taiwan

It remains unclear whether androgen deprivation therapy (ADT) is associated with subsequent dementia risk in patients with prostate cancer. There are limited data regarding dementia risk across ADT types. To examine the association between all-cause dementia, including Alzheimer disease (AD), and different ADT types in patients with prostate cancer. This cohort study used linked data from the Taiwan National Cancer Registry, the National Health Insurance Research Database, and the Taiwan National Death Registry. A cohort of 23 651 patients with newly diagnosed prostate cancer between January 1, 2008, and December 31, 2015, was identified and followed up from 1 year after diagnosis until December 31, 2017. Data analysis was performed between January 2019 and May 2020. Patients who received and did not receive ADT, including gonadotropin-releasing hormone (GnRH) agonists, orchiectomy, or antiandrogen monotherapy. The primary outcomes were all-cause dementia or AD. Stabilized inverse probability of treatment weighting was used to balance baseline covariates. The association between dementia and various ADT types was examined using the Cox proportional hazards model. Furthermore, a multivariate Cox proportional model with age as the time scale was conducted for complementary comparison. In the cohort of 23 651 male patients (median [interquartile range] age, 73 [66-79] years), 6904 (29.2%) did not receive ADT, 11 817 (50.0%) received GnRH agonists, 876 (3.7%) received orchiectomy, and 4054 (17.1%) received antiandrogen monotherapy. Overall, 1525 patients were diagnosed with incident dementia (1.72 per 100 person-years) during a median (interquartile range) follow-up of 3.46 (1.92-5.51) years. Compared with those who did not receive ADT, those using antiandrogen monotherapy showed an increased risk of dementia (weighted hazard ratio [HR], 1.34; 95% CI, 1.16-1.55) and AD (weighted HR, 1.52; 95% CI, 1.13-2.04). The risk of dementia was similar between GnRH agonist use or orchiectomy and no ADT use (GnRH agonist: weighted HR, 1.13; 95% CI, 1.00-1.28; orchiectomy: 1.00; 95% CI, 0.74-1.37). Several sensitivity analyses revealed consistent findings for both outcomes. In this study, the use of antiandrogen monotherapy was associated with increased risk of dementia or AD, while GnRH agonist use and orchiectomy had no significant difference compared with patients who did not receive ADT. Further prospective studies are warranted to confirm these findings.

Alleviation of Symptoms and Improvement of Endometrial Receptivity Following Laparoscopic Adenomyoma Excision and Secondary Therapy with the Levonorgestrel-releasing Intrauterine System.

To assess the treatment efficacy of adenomyoma and improvement in implantation receptivity associated with the levonorgestrel-releasing intrauterine system (LNG-IUS) combined with adenomyoma resection. Fifty subjects (control group) underwent laparoscopic adenomyoma excision and received gonadotropin-releasing hormone (GnRH) agonists, and 201 subjects (experimental group) underwent laparoscopic adenomyoma resection and received GnRH agonists combined with the LNG-IUS. Pipelle endometrial biopsies were obtained in the mid-luteal phase, before the operation, and 19months after the operation. Menstrual blood loss was measured using a pictorial blood loss assessment chart. Pain intensity during menstruation was evaluated on a 10-point visual analog scale (VAS). The volume of uterus was measured through ultrasound. Quantification of HOXA10 promoter methylation was performed through bisulfite sequencing polymerase chain reaction (BSP). Real-time polymerase chain reaction analyzed the expression levels of endometrial HOXA10-mRNA and leukemia inhibitory factor (LIF)-mRNA. After surgery, the scores for dysmenorrhea and menorrhagia were significantly improved, and the volume of the uterus was obviously reduced (all p < 0.01). The mean number of methylated CpG sites, level of endometrial HOXA10-mRNA, and level of endometrial LIF-mRNA were 5.6 ± 1.7 versus 3.9 ± 1.3, 0.8 ± 0.2 versus 0.9 ± 0.3, and 0.8 ± 0.2 versus 1.0 ± 0.2, respectively, in the control group versus the experimental group at 19months after surgery, and significant improvements were observed in the experimental group (p < 0.001, p = 0.034, p < 0.001). Laparoscopic adenomyoma excision and GnRH agonists can alleviate the symptoms, reduce the number of methylated CpG sites in HOXA10, and improve endometrial HOXA10-mRNA and endometrial LIF-mRNA levels. When combined with subsequent use of the LNG-IUS, better efficacy can be achieved.

Utilization of gonadotropin-releasing hormone agonists for preservation of ovarian function in women with breast cancer receiving chemotherapy

To determine the use and predictors of GnRH (gonadotropin-releasing hormone) agonists for ovarian conservation in young, reproductive age women with newly diagnosed breast cancer undergoing chemotherapy. Retrospective cohort study. The MarketScan database was used to identify women 15-45 years of age with newly diagnosed breast cancer from 2008-2017. All patients underwent cancer directed surgery (lumpectomy, mastectomy, biopsy or lymph node evaluation) and received cytotoxic chemotherapy within three months before or after surgery. Patients were considered to have received GnRH agonist therapy if they had one claim for a GnRH agonist in the same period. All women with history of oophorectomy before or during the study period were excluded from the study. Trends and predictors of GnRH agonist use were described and compared using Cochran-Armitage trend test and Chi-square tests. We identified a total of 13,634 women with breast cancer who underwent treatment with chemotherapy. The median age was 39 years with 755 women <30 (5.5%) years of age and 12,879 >30 (94.5%) years old. GnRH agonists were administered to 112 (0.8%, 95% CI 0.7-1.0%) women. The rate of GnRH agonist use was higher in women age 15-30 years compared to women age 30-45 (2.8% vs 0.7%) (P< 0.001). During the study period, the utilization of GnRH agonists increased from 0.3% in 2008 to 1.3% in 2017 (P<0.001). Use of GnRH agonists was higher in the Northeast (2.0%) compared to the north central (0.7%), southern (0.6%) and western (0.5%) U.S. (P<0.001). The utilization of GnRH agonists among reproductive age women with breast cancer undergoing chemotherapy is extremely low.

Ovarian protection and fertility preservation in women with cancer: A French national registry analysis between 2005 and 2014

ObjectiveOvarian failure is a common effect of treatment for cancer. The aim of this study was to describe the practices concerning ovarian protection and fertility preservation in young women treated for cancer. Study designWomen between 15 and 49 years old diagnosed with cancer between 2005 and 2014 were studied, abstracted from a representative French National Healthcare database. To assess practices concerning ovarian protection, gonadotropin-releasing hormone (GnRH) agonist consumption and ovarian transposition were analyzed. For fertility preservation, GnRH agonist consumption, ovarian cryopreservation and oocyte cryopreservation were analyzed. Explanatory variables were analyzed using a multilevel model. ResultsA total of 2447 women were identified. Among the 553 patients exposed to ovarian failure, 74 (13%) had ovarian protection (67 received GnRH agonists, 7 underwent ovarian transposition). Among the 227 women exposed to fertility alteration, 53 (23%) had fertility preservation (37 received GnRH agonists, 16 had ovarian or oocyte cryopreservation). Factors associated with ovarian protection were age under 40 years old (OR = 1.56 [1.5–1.62], p = 0.006) and diagnosis of breast cancer (OR = 1.15 [1.08–1.22], p < 0.001). The only factor associated with fertility preservation was breast cancer (OR = 1.17 [1.1–1.24], p < 0.001). The five-year probability of pregnancy was 3.8% and 9.8% (p = 0.26) for women with and without fertility preservation, respectively. ConclusionOver the last decade, ovarian protection and fertility preservation concerned 13% and 23%, respectively, of young French women treated for cancer. Awareness about ovarian protection and fertility preservation remain insufficient and need to be extended to improve this major aspect of cancer management.

Frozen thawed embryo transfer cycles; A comparison of pregnancy outcomes with and without prior pituitary suppression by GnRH agonists: An RCT

To perform an in-vitro fertilization cycle, pretreatment with gonadotropin-releasing hormone (GnRH) agonist is widely used as a part of controlled ovarian hyper-stimulation protocols to prevent endogenous luteinizing hormone surge and spontaneous ovulation. GnRH agonist pretreatment is relatively costly and there is a risk of hypo estrogenic side effect. It would also lengthen the preparation period until pituitary desensitization occurs. Our study is aimed at evaluating the pregnancy outcome rate of frozen thawed embryo transfer with and without GnRH agonists pretreatment. Women with documented infertility who were candidate for frozen thawed embryo transfer were recruited and randomly assigned to two groups. In group A (n=100), patients received GnRH agonist, Buserelin, to induce pituitary desensitization prior to endometrial preparation and embryo transfer. Individuals in group B (n=100) received steroid manipulation without prior down-regulation of the pituitary. Chemical pregnancy, implantation rate, clinical pregnancy and ongoing pregnancy were measured and statistically compared between the two groups. None of the outcome measures including clinical and chemical pregnancy rates, implantation rate, and ongoing pregnancy rate showed significant difference between the two groups. Similarly, the rate of miscarriage did not vary between the two groups. In this study, we found that removing the GnRH agonists pretreatment from the programmed cycles did not negatively influence the pregnancy outcome or implantation rate. Moreover, it will cause a considerable reduction in cost of assisted reproductive technology as well as adverse effects related to GnRH agonists, while having a favorable implantation and pregnancy outcomes.

Fertility Sparing Treatment in Patients With Early Stage Endometrial Cancer, Using a Combination of Surgery and GnRH Agonist: A Monocentric Retrospective Study and Review of the Literature.

Objectives: To evaluate the efficacy and safety of gonadotropin-releasing hormone (GnRH) agonist after endometrial resection in women suffering early stage endometrial carcinoma (EC) and/or endometrial intra-epithelial neoplasia (EIN).Design: A retrospective review of clinical files between January 1999 and December 2016.Setting: University hospital.Patients: Eighteen women younger than 41 years with grade 1 endometrial carcinoma (G1EC) and/or Endometrial intra-epithelial neoplasia (EIN). Interventions: All patients received GnRH agonist for 3 months after an endometrial resection combined with a laparoscopy to exclude concomitant ovarian tumor and/or other extra-uterine disease. The patient underwent a follow-up of 3 months interval with endometrial sampling by hysteroscopy.Main Outcome Measure(s): The recurrence rate and the pregnancy rate after fertility sparing treatment.Results: We identified 9 patients with EIN (50%), 7 patients with G1EC (38.9%), 1 with combined histology (5.5%), and 1 with G2EC (5.5%). After a median follow-up of 40.7 months, 12 patients conserved their uterus (66.7%), and 8 (53.3%) patients were pregnant with a total of 14 pregnancies among those who tried to become pregnant. We observed a complete response rate in 12 patients (66.7%) but 3 of these patients relapsed (25%). We also found a stable disease in 6 patients (33.3%).Conclusions: Compared with other fertility sparing treatments, GnRH agonist after surgery is an effective fertility-sparing strategy for women with EIN and/or G1EC. We recommend hysterectomy once a family has been completed even if the literature does not clearly lead to radical surgery.

Quality of life and psychosocial and physical well-being among 1,023 women during their first assisted reproductive technology treatment: secondary outcome to a randomized controlled trial comparing gonadotropin-releasing hormone (GnRH) antagonist and GnRH agonist protocols

To compare self-reported quality of life, psychosocial well-being, and physical well-being during assisted reproductive technology (ART) treatment in 1,023 women allocated to either a short GnRH antagonist or long GnRH agonist protocol. Secondary outcome of a prospective phase 4, open-label, randomized controlled trial. Four times during treatment a questionnaire on self-reported physical well-being was completed. Further, a questionnaire on self-reported quality of life and psychosocial well-being was completed at the day of hCG testing. Fertility clinics at university hospitals. Women referred for their first ART treatment were randomized in a 1:1 ratio and started standardized ART protocols. Gonadotropin-releasing hormone analogue; 528 women allocated to a short GnRH antagonist protocol and 495 women allocated to a long GnRH agonist protocol. Self-reported quality of life, psychosocial well-being, and physical well-being based on questionnaires developed for women receiving ART treatment. Baseline characteristics were similar, and response rates were 79.4% and 74.3% in the GnRH antagonist and GnRH agonist groups, respectively. Self-reported quality of life during ART treatment was rated similar and slightly below normal in both groups. However, women in the GnRH antagonist group felt less emotional (adjusted odds ratio [AOR] 0.69), less limited in their everyday life (AOR 0.74), experienced less unexpected crying (AOR 0.71), and rated quality of sleep better (AOR 1.55). Further, women receiving GnRH agonist treatment felt worse physically. Women in a short GnRH antagonist protocol rated psychosocial and physical well-being during first ART treatment better than did women in a long GnRH agonist protocol. However, the one item on self-reported general quality of life was rated similarly. NCT00756028.

Gonadotropin-releasing Hormone Agonists, Orchiectomy, and Risk of Cardiovascular Disease: Semi-ecologic, Nationwide, Population-based Study

BackgroundIn observational studies, men with prostate cancer treated with gonadotropin-releasing hormone (GnRH) agonists had a higher risk of cardiovascular disease (CVD) compared to men who had undergone orchiectomy. However, selection bias may have influenced the difference in risk. ObjectiveTo investigate the association of type of androgen deprivation therapy (ADT) with risk of CVD while minimising selection bias. Design, setting, and participantsSemi-ecologic study of 6556 men who received GnRH agonists and 3330 men who underwent orchiectomy as primary treatment during 1992–1999 in the Prostate Cancer Database Sweden 3.0. Outcome measurements and statistical analysisWe measured the proportion of men who received GnRH agonists as primary treatment in 580 experimental units defined by healthcare provider, diagnostic time period, and age at diagnosis. Incident or fatal CVD events in units with high and units with low use of GnRH agonists were compared. Net and crude probabilities were also analysed. Results and limitationsThe risk of CVD was similar between units with the highest and units with the lowest proportion of GnRH agonist use (relative risk 1.01, 95% confidence interval [CI] 0.93–1.11). Accordingly, there was no difference in the net probability of CVD after GnRH agonist compared to orchiectomy (hazard ratio 1.02, 95% CI 0.96–1.09). The 10-yr crude probability of CVD was 0.56 (95% CI 0.55–0.57) for men on GnRH agonists and 0.52 (95% CI 0.50–0.54) for men treated with orchiectomy. The main limitation was the nonrandom allocation to treatment, with younger men with lower comorbidity and less advanced cancer more likely to receive GnRH agonists. ConclusionOur data do not support previous observations that GnRH agonists increase the risk of CVD in comparison to orchiectomy. Patient summaryWe found a similar risk of cardiovascular disease between medical and surgical treatment as androgen deprivation therapy for prostate cancer.

Is Menstruation or the Serum Hormone Level a Useful Predictor for Live Birth after Gonadotropin-Releasing Hormone Agonist during Chemotherapy in Young Breast Cancer Patients

Aims: The study aimed to investigate whether changes in menstruation or hormone levels are useful parameters to assess the efficacy of gonadotropin-releasing hormone (GnRH) agonist co-treatment with chemotherapy. Methods: This study included women in their reproductive age diagnosed with breast cancer and who received GnRH agonist during chemotherapy for ovarian protection. Women with treatment failure (follicle-stimulating hormone (FSH) level >20 mIU/mL after at least 12 months and failure for becoming pregnant; n = 16) or with treatment success (becoming pregnant spontaneously and having a live birth; n = 20) were selected, and clinical characteristics, resumption of menstruation, and changes in hormone profiles were compared. Results: Resumption of menstruation was observed in 8 (50%) women and the time until resumption was significantly longer in the treatment failure group. Although levels of luteinizing hormone (LH) and FSH at 3 and 6 months after chemotherapy did not differ between the groups, serum FSH levels were significantly higher in the treatment failure group at 12 months. However, levels of LH or estradiol were not different at each time point. Conclusion: Changes in menstruation and FSH levels at 12 months or longer may be useful parameters to predict successful spontaneous pregnancy and live birth after GnRH agonist co-treatment for ovarian protection in young breast cancer patients who undergo chemotherapy.

Repeated doses of GnRH antagonist at midcycle in artificial frozen embryo transfer cycles may not affect pregnancy outcomes

No significant differences in outcomes have been found between protocols of endometrial preparation for frozen embryo transfer (FET), though gonadotropin releasing hormone (GnRH) antagonists may have detrimental effects on the endometrium. We conducted a retrospective cohort noninferiority study at a single academic center of women receiving multiple doses of mid-cycle GnRH antagonist (GAnt) to those receiving GnRH agonist (GAg) to determine if there are detrimental effects of GnRH antagonists. 1047 FET cycles were identified, detailed data was available in 840 cycles: 610 GAg and 230 GAnt cycles. Patients undergoing GAnt cycles were older (40 ± 6.6 versus 37 ± 5.1 years, p < 0.0001), more often used donor oocyte (36% versus 18.6%, p < 0.0001), and more often exhibited diminished ovarian reserve (49.1% versus 36.2%, p = 0.0009). Clinical pregnancy rates (CPRs) per transfer and implantation rates (IRs) were similar for GAnt and GAg cycles. There was a trend for higher pregnancy and IRs with GAg cycles in younger women (CPR 38.8% versus 26.7%, p = 0.16; IR 36% versus 23.3%, p = 0.07). Stratifying by diagnosis, CPR and IR were similar in GAnt and GAg cycles. A GAnt protocol of endometrial preparation for FET is not inferior to a GAg protocol regardless of patient age, use of donor oocyte, or infertility diagnosis.

The age-related recurrence of endometrioma after conservative surgery

ObjectiveAs endometrioma frequently recurs after conservative surgery, long-term postoperative medical treatment for the prevention of recurrence is necessary. However, it has not been elucidated whether long-term postoperative medical treatment is crucial to all patients until menopause. Thereupon, this study was conducted to evaluate the age-related recurrence patterns after conservative surgery for endometrioma. Study designA retrospective cohort study was performed on a total of 420 reproductive-aged women who underwent conservative surgery for endometrioma between January 2000 and December 2010. Ultrasonography was used during the follow-up period to detect endometrioma recurrence. Patients were classified into two groups according to the use of postoperative medications. The first group was observation only, while the second received gonadotropin releasing hormone agonists followed by cyclic oral contraceptives. The cumulative recurrence rate of endometrioma was compared according to the age at surgery (20–29 years, 30–39 years, 40–45 years) within each group. Subgroup analysis was performed according to the age between the two groups. ResultsThe median follow-up duration after surgery was 29.0 months (range 6–159 months) for all patients. After adjusting for parity, size and bilaterality of cyst, and stage with American Society for Reproductive Medicine classification of endometriosis which was statistically different, within the group of no treatment, the cumulative recurrence rate in 40–45 years (10.2%) was significantly lower compared with those in 20–29 years (43.3%; hazard ratio (HR)=0.04; 95% confidence interval (CI)=0.01–0.52) and 30–39 years (22.5%; HR=0.19; 95% CI=0.04–0.92). However, there were no differences within the group of postoperative medical treatment. When we compared between the two groups, the cumulative recurrence rate was significantly different in 20–29 years (8.1 vs 43.3%; p<0.001) and 30–39 years (5.4 vs 22.5%; p=0.007), but there was no difference in 40–45 years (4.5 vs 10.2%; p=0.901). ConclusionsOur preliminary results demonstrate that the risk of endometrioma recurrence decreases with age. After the age of forty, the recurrence rate does not differ according to the use of postoperative medication. Based on our results, postoperative medical treatment may be individualized according to the patient’s age at the time of surgery. Further studies are needed to identify patients who may benefit from postoperative medication.

Association between duration and type of androgen deprivation therapy and risk of diabetes in men with prostate cancer.

Androgen deprivation therapy (ADT) for prostate cancer (PCa) increases risk of type 2 diabetes (T2DM); however the association between types and duration of ADT has not been fully elucidated. We examined how type and duration of ADT affects risk of T2DM. Using data from Prostate Cancer database Sweden (PCBaSe) we investigated risk of T2DM in a cohort of 34,031 men with PCa on ADT; i.e., anti‐androgens (AA), orchiectomy, or gonadotropin‐releasing hormone (GnRH) agonists compared to an age‐matched, PCa‐free comparison cohort (n = 167,205) using multivariate Cox proportional hazard regression. T2DM was defined as a newly filled prescription for metformin, sulphonylurea, or insulin in the Prescribed Drug Register. A total of 21,874 men with PCa received GnRH agonists, 9,143 AA and 3,014 underwent orchiectomy. Risk of T2DM was increased in men in the GnRH agonists/orchiectomy group during the first 3 years of ADT [i.e., 1 − 1.5 years HR: 1.61 (95%CI: 1.36 − 1.91)], compared to PCa‐free men. The risk decreased thereafter (e.g., 3 − 4 years HR: 1.17 (95% CI: 0.98 − 1.40)). Conversely, no increased risk was seen in men on AA (HR: 0.74 (95%CI: 0.65 − 0.84). The incidence of T2DM per 1,000 person‐years was 10 for PCa‐free men, 8 for men on AA, and 13 for men on GnRH agonists/orchiectomy. Duration of ADT has a significant impact on risk of T2DM. With the peak after three years of treatment, our data indicates that men on ADT, even for a limited period of time, such as adjuvant to radiotherapy, are at increased risk of T2DM.

Abstract P5-13-06: Concurrent gonadotropin-releasing hormone (GnRH) agonist administration with chemotherapy improves neoadjuvant chemotherapy responses in young premenopausal breast cancer patients

Abstract Background Gonadotropin-releasing hormone (GnRH) agonist therapy for ovarian function preservation shows promising results. This study aimed to determine the oncologic efficacy of GnRH agonist treatment concurrent with chemotherapy in a neoadjuvant setting. Patients and Methods A retrospective analysis was performed on 332 cases of invasive breast cancer in patients who were &amp;lt;40 years old at diagnosis and received GnRH agonists concurrent with neoadjuvant chemotherapy (GnRH agonist group) or neoadjuvant chemotherapy alone (neochemotherapy-alone group) at Asan Medical Center from December 2010 to September 2014. Pathologic complete response rates (pCR) and Ki-67 changes were evaluated between the two groups. For hormone receptor (HR)-positive tumors, the clinical response and preoperative endocrine prognostic index (PEPI) score also were evaluated. Results The median age was 32 ± 3.9 and 36 ± 3.0 years old in the GnRH agonist group and neochemotherapy-alone group, respectively (P &amp;lt; .001). Adjusted for tumor size, grade, lymph node metastasis, HR status, and chemotherapy regimen, the GnRH agonist group exhibited a higher pCR rate with an odds ratio (OR) of 2.98 (95% CI, 1.37–6.34) and more decreased Ki-67 expression during treatment (P = 0.05) than the neochemotherapy-alone group. In HR-negative tumors, the GnRH agonist group showed a higher pCR rate (multivariate OR = 3.50; 95% CI, 1.37–8.95) and more decreased Ki-67 expression (P = 0.047). In HR-positive breast cancer, the pCR rate, change in Ki-67 index, and clinical response were higher and preoperative prognostic index (PEPI) scores were lower in the GnRH agonist group, but not significant between the two treatment groups. Conclusion Concurrent administration of GnRH agonists during neoadjuvant chemotherapy improved pCR rates and suppressed Ki-67 expression especially in HR-negative tumors. Citation Format: Yoon TI, Kim HJ, Yu JH, Sohn G, Ko BS, Lee JW, Son BH, Ahn SH. Concurrent gonadotropin-releasing hormone (GnRH) agonist administration with chemotherapy improves neoadjuvant chemotherapy responses in young premenopausal breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-13-06.

Effect of gonadotropin-releasing hormone agonist therapy on body mass index and growth in girls with idiopathic central precocious puberty.

Objective:The study aimed to assess the effect of gonadotropin-releasing hormone (GnRH) agonist therapy on body mass index (BMI) and growth in girls diagnosed with idiopathic central precocious puberty (CPP).Materials and Methods:Hospital records of 32 girls with idiopathic CPP who have been receiving GnRH agonist therapy for at least 12 months were retrospectively reviewed and auxological, clinical and laboratory parameters of the patients were recorded. BMI, body mass index standard deviation score (BMI SDS) for chronological age body mass index standard deviation score (CA-BMI SDS), BMI SDS for bone age body mass index standard deviation score (BA-BMI SDS), ratios of obesity and overweight were assessed before treatment and on the 12th month of therapy in patients diagnosed with idiopathic CPP.Results:The study comprised of 32 girls diagnosed with idiopathic CPP. BMI values showed statistically significant increase in the 1st year of treatment (19.16 ± 2.8 vs. 20.7 ± 3.4, P = 0.001). Despite a mild increase in CA-BMI SDS in the 1st year of treatment versus before treatment, it was no statistically significant (1.0 ± 0.8 vs. 1.1 ± 0.9, P = 0.061). However, significant increase was observed in BA-BMI SDS in the 1st year of treatment versus before treatment (0.8 ± 0.7 vs. 0.4 ± 0.8, P < 0.001). Before treatment, 37.5% (12/32) of the patients were overweight and 21.9% (5/32) were obese, whereas in the 1st year, 34.4% (11/32) of the patients were overweight and 31.3% were obese (P = 0.001).Conclusion:Whilst 1/3 of the cases diagnosed with idiopathic CPP were overweight and obese at the time of diagnosis, GnRH agonist therapy caused statistically significant weight gain in patients diagnosed with CPP. Therefore, these patients should be closely monitored and weight control should be provided by diet and exercise programs in the course of treatment.