Releasing Hormone Antagonist Research Articles

Effects of Luteinizing Hormone Supplementation on Ovarian Response and Assisted Reproductive Technology Outcomes in Antagonist In vitro Fertilization/Intracytoplasmic Sperm Injection Cycles: A Meta-analysis

Objective: The study objective was to investigate the effects of luteinizing hormone (LH) supplementation on ovarian response and assisted reproductive technology (ART) outcomes in in vitro fertilization/intracytoplasmic sperm injection cycles with a gonadotropin (Gn)-releasing hormone antagonist protocol. Methods: This is a meta-analysis, and nine published randomized controlled trials (1,685 patients) were included. Continuous data were extracted in the form of mean ± standard deviation and population size, whereas dichotomous data were extracted in the form of odds ratio. Results: The total amount of follicle-stimulating hormone (FSH) used, the duration of stimulation (DOS), the number of eggs in MII stage, the total number of formed embryos, the clinical pregnancy rate, and live birth rates were similar between groups, but the estrogen level on the day of human chorionic Gn (hCG) administration was slightly higher in the LH supplementation group. On subgroup analysis, it was reported that the addition of LH could significantly increase estrogen levels on the day of hCG administration in patients older than 35 years, and LH supplementation starting on the day of FSH administration may slightly extend the DOS. Moreover, regardless of the timing of LH supplementation, an increase in estrogen levels was found on the day of hCG administration. Conclusions: LH supplementation of an antagonist protocol increases estrogen levels on the day of hCG administration, but does not increase the number of mature oocytes retrieved, and also fails to improve ART outcomes.

Effect of short‐term 17B‐estradiol on low‐flow‐mediated constriction in young women

Low‐flow mediated constriction (L‐FMC) examines vascular responses during a reduction in blood flow and provides a measure of resting shear‐stress dependent vascular tone. L‐FMC is a complementary measure to flow‐mediated dilation (FMD), and is blunted in patients with cardiovascular disease. 17β‐estradiol (E2) exerts positive effects on vascular endothelial health and can improve FMD. However, it is unknown whether E2 impacts L‐FMC.PURPOSEThe purpose of this study was to test the hypothesis that E2 administration would augment L‐FMC in young women.METHODSEleven young women (24±1 years, 24±1 kg/m2) have completed the study. To isolate the impact of E2, endogenous ovarian hormone production was suppressed with daily subcutaneous injections of a gonadotropin releasing hormone antagonist (GnRHant, 0.25 mg/day) for 10 days. E2 (0.1mg/day patch) was administered during the last 7 days of GnRHant. We measured changes in brachial artery diameter via ultrasound on day 3 of GnRHant and day 7 of E2 add‐back. A blood pressure cuff was placed just distal to the olecranon process and inflated to 200mmHg for five minutes. Images were recorded continuously at baseline (1‐minute), during occlusion (5‐minutes), and after cuff deflation (2‐minutes). L‐FMC was determined from the last 30 seconds of cuff inflation using the lowest average value and was reported as percent change from baseline diameter. FMD was calculated as a percent change from baseline to peak diameter after cuff deflation. Total vessel reactivity was calculated as the absolute value of L‐FMC and FMD. Results are reported as mean ± standard error.RESULTSBaseline diameter was similar between GnRHant (3.14 ± 0.12 mm) and E2 (3.08 ± 0.11 mm; p=0.3). L‐FMC tended to be greater during E2 administration (GnRHant −2.5 ± 0.5% vs. E2 −3.8 ± 0.5%; p=0.11). However, FMD (GnRHant 7.5 ± 0.7% vs. E2 7.6 ± 1.1%; p=0.92) and total vessel reactivity (GnRHant 10.0 ± 0.7% vs. E2 11.5 ± 1.2%; p=0.26) were not altered by E2.CONCLUSIONThese preliminary findings suggest that short term E2 administration may augment L‐FMC in young women. Additional data are needed to understand the impact of ovarian hormones on L‐FMC and its role in regulating vascular health.Support or Funding InformationNIH Grant P20 GM 103446, P20 GM 113125, U54 GM 104941, The University of Delaware Research Foundation, and AHA Award 16SDG30700015This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Gonadotropin releasing hormone antagonist use in controlled ovarian stimulation and intrauterine insemination cycles in women with polycystic ovary syndrome

ObjectiveTo evaluate the effect of the GnRH antagonist on gonadotropin ovulation induction in women with PCOS. Materials and methodsA total of 175 intrauterine insemination (IUI) cycles in women with polycystic ovary syndrome (PCOS) were included in the study. Women in the control group (n = 87) underwent controlled ovarian stimulation (COS) with recombinant follicle stimulating hormone (r-FSH) only, while women in the study group (n = 88) were administered r-FSH plus cetrorelix. ResultsAs expected, the mean value of luteinizing hormone and progesterone, on the day of human chorionic gonadotropin administration were statistically significantly lower in patients receiving GnRH antagonist than the control group (p = 0.002). Premature luteinization occurred in only one of the patients in the GnRH antagonist group (1.1%) and in 15 of the 88 cycles in the control group (17.2%), showing a significant difference between the two groups (P = 0.001). The clinical pregnancy rate per cycle was higher in GnRH-antagonist group compared to the control group but the difference did not reach to a statistical significance (25% vs 14.9%, P = 0.096). ConclusionsAdding GnRH-antagonist in COS/IUI cycles in women with PCOS resulted in a lower incidence of premature luteinization but did not improve pregnancy rates. However, owing to some benefits, antagonist therapy could be considered as a reasonable alternative to IVF in order to reduce PCOS patients'emotional distress.

Association between progesterone to number of mature oocytes index and live birth in GnRH antagonist protocols.

What is the association between blood progesterone level alone, progesterone to mature oocytes index (PMOI) and IVF outcomes? Clinical data from 960 couples undergoing their first fresh embryo transfer after an intracytoplasmic sperm injection attempt carried out between September 2012 and July 2017 were analysed. All patients underwent ovarian stimulation combining recombinant FSH and gonadotrophin releasing hormone antagonist. Progesterone was measured on the day on which ovulation was triggered. The PMOI was divided into four groups based on 25th, 50th and 75th percentiles, and live birth and implantation rates were compared between the groups. A negative association was found between PMOI levels, live birth and implantation rates. When adjusting for age, ovarian stimulation index (OSI) and number of embryos transferred, the PMOI remained negatively correlated to live birth rate (LBR) (OR = 0.147 [0.031 to 0.701]; P = 0.0161), whereas total blood progesterone was no longer evident. Moreover, the LBR (18.5% versus 28.4%; P < 0.01) and implantation rate (12.4% versus 21.0%; P < 0.01) were significantly decreased only when PMOI was 0.167 ng/ml or greater, irrespective of progesterone concentration (< or ≥1.08 ng/ml). The opposite was not true, however. Similar PMOIs were recorded in the same patient from one attempt to the next, and were partially linked to basal FSH, anti-Müllerian hormone, antral follicle count and OSI. PMOI seems to be more predictive than total progesterone level of IVF outcome and reflects the ability of embryos to develop as it is linked to the implantation rate.

PGR and PTX3 gene expression in cumulus cells from obese and normal weighting women after administration of long-acting recombinant follicle-stimulating hormone for controlled ovarian stimulation.

The present study aimed to determine clinical IVF parameters and gene expression in cumulus cells (CCs) in obese and normal weighting women after administration of 150mcg of corifollitropin alfa for controlled ovarian hyperstimulation (COH). 150mcg of corifollitropin alfa and gonadotropin releasing hormone antagonist were used for COH. Analysis of CC gene expression was performed using quantitative real-time PCR. We did not find significant differences in biochemical and clinical pregnancy rates between obese and normal weighting women. Obese women required twice as much of additional gonadotropins for ovarian stimulation and had a significantly lower proportion of good quality embryos on day 5 of IVF cycle. Expression of PGR and PTX3 was significantly higher in CCs of obese women. Obese women require significantly larger amounts of gonadotropins to achieve similar IVF success rates as normal weighting women. Differences in CC gene expression and smaller proportion of good quality embryos may imply that oocytes derived from obese women are of lower quality. Further studies are needed to evaluate whether obesity itself or the higher amount of gonadotropins used in obese women causes this effect.

Impact of Serum Progesterone Levels in GnRH Antagonist Assisted Reproduction Cycles on Pregnancy Outcomes: A Prospective Cohort Study

Background: With controlled ovarian hyperstimulation (COH) with gonadotrophin releasing hormone (GnRH) antagonists, sometimes it is associated with incomplete luteolysis leading to elevated serum progesterone in early follicular phase. Persistence of this elevation might reduce the chance for clinical pregnancy. Objective: To assess the effect of elevated early and late follicular progesterone (P) levels during gonadotrophins releasing hormone (GnRH) antagonist cycles on pregnancy outcome. Design: Prospective single center study. Setting: North-western Military hospital, Kingdom of Saudi Arabia. Patients: 302 in vitro fertilization/intra-cytoplasmic sperm injection (IVF-ICSI) patients. Intervention(s): Recombinant follicle stimulating hormone (r-FSH), (150 - 300 IU) started daily from cycle day 2; GnRH antagonist treatment started on day 6 of the cycle. The serum progesterone (P) measured twice on cycle day 2 and human chorionic gonadotrophin (hCG) day. Main Outcome Measures: Clinical pregnancy and live birth rates per started cycle. Results: The incidence of elevated serum P on day 2 was (5.3%) and on hCG day was (17.5%), statistically significant differences in clinical pregnancy rate (32.3% versus 13.0%) and in live birth rate (23.4% versus 11.1%) were present between the normal and high serum progesterone groups on hCG day, but these differences were not statistically significant in the groups of elevated basal progesterone. Conclusion: Follicular phase progesterone rise either on day 2 or the day of hCG trigger was associated with lower clinical pregnancy and live birth rates. This impact was more prominent with trigger day elevation.

Endometrium cytokine profiles are altered following ovarian stimulation but almost not in subsequent hormone replacement cycles

PurposeTo investigate the impact of ovarian stimulation and hormone replacement treatment on key regulatory cytokines in endometrial secretion during endometrium implantation window. MethodsFifty-six patients undergoing ovarian stimulation (OS) with gonadotropin releasing hormone antagonist and frozen embryo transfer with hormone replacement treatment (HRT) were recruited. Endometrial secretion aspiration was performed repeatedly during implantation window in natural, OS and HRT cycles of every patient. The concentrations of 17 mediators, known to be involved in human embryo implantation, were assessed by multiplex immunoassay. ResultsCompared with natural cycle (NC), the concentration of IFN-γ, G-CSF and IL-8 within endometrium were almost the same following OS and HRT. Furthermore, increased MCP-1 levels were observed following HRT and OS. In addition, an increase in IL-1b, IL-7, IL-17, IL-6, TNF-a, IL-12, IL-4, IL-13, IL-10, IL-5, VEGF and MIP-1b concentrations were found in OS cycle only. The level of GM-CSF was lower in HRT cycle and higher in OS cycle, when compared with NC. Among all 17 cytokines, no correlation was found between cytokine concentrations and serum estradiol and progesterone, while only IL-7 concentration has a low correlation with serum LH level. ConclusionCompared to natural and hormone replacement cycle, patients’ endometrium cytokine profiles present an increased inflammatory response following ovarian stimulation.

FSH suppression and tumour control in patients with prostate cancer during androgen deprivation with a GnRH agonist or antagonist

Background: Gonadotropin releasing hormone (GnRH) antagonists suppress follicle-stimulating hormone (FSH) to lower levels than GnRH agonists. This may partially explain the differences between these agents on prostate cancer outcomes. In this post-hoc analysis, FSH and prostate specific antigen (PSA) responses and the impact of cross-over from leuprolide to degarelix were evaluated from a 1-year comparative study (CS21) and its extension study (CS21A).Materials and methods: Overall, 610 patients were enrolled in CS21, wherein PSA and FSH levels were evaluated monthly. CS21A evaluated 386 patients, including those previously treated with degarelix (n = 251) who continued to receive degarelix, and those previously treated with leuprolide (n = 135) who crossed-over to receive degarelix. PSA and FSH levels were evaluated in CS21A for 3 months after cross-over. The associations between measurements were assessed using Spearman’s correlation coefficient. The impact of class variables on FSH suppression were evaluated using Analysis of Variance.Results: Rapid PSA and FSH suppression was observed and maintained in the degarelix arm (CS21 and CS21A), while patients on leuprolide experienced rising PSA during CS21. Patients crossed-over from leuprolide to degarelix achieved a suppression of FSH and a significant PSA decrease. PSA and FSH levels were significantly (p < .05) correlated at months 1, 3, 6, 12 and 13 in the degarelix arm.Conclusions: Significant FSH suppression with GnRH antagonists may explain its advantage over GnRH agonists in terms of better prostate cancer control. The effect of profound FSH suppression is analogous to the need for profound testosterone suppression for tumor control.

Effect of corticotropin releasing hormone and corticotropin releasing hormone antagonist on biosynthesis of gonadotropin relasing hormone and gonadotropin relasing hormone receptor in the hypothalamic-pituitary unit of follicular-phase ewes and contribution of kisspeptin.

This study aimed to determine the mechanisms governing Gonadotropin releasing hormone (GnRH) biosynthesis and luteinising hormone (LH) secretion in follicular-phase sheep after infusion of corticotropin releasing hormone (CRH) and/or CRH antagonist corticotropin releasing hormone nist (CRH-A) into the third cerebral ventricle. The study included two experimental approaches: first, we investigated the effect of CRH or CRH-A (α-helical CRH 9-41) on GnRH and GnRH receptor (GnRHR) biosynthesis in the preoptic area (POA), anterior (AH) and ventromedial hypothalamus (VMH), stalk/median eminence (SME), and on GnRHR in the anterior pituitary (AP) using an enzyme-linked immunosorbent assay (ELISA); second, we used real-time PCR to analyse the influence of CRH and CRH-A on the levels of kisspeptin (Kiss1) mRNA in POA and VMH including arcuate nucleus (VMH/ARC), and on Kiss1 receptor (Kiss1r) mRNA abundance in POA-hypothalamic structures. These analyses were supplemented by radioimmunoassay (RIA) and ELISA methods for measurement of LH and cortisol levels in the blood, respectively. Our results show that administration of CRH significantly decreased GnRH biosynthesis in the POA/hypothalamus. CRH also decreased GnRHR abundance in the hypothalamus and in the AP, but increased it in the POA. Furthermore, administration of CRH decreased plasma LH concentration and levels of Kiss1 mRNA in the POA and VMH/ARC as well as Kiss1r mRNA in these structures and in the SME. Significant increase in plasma cortisol concentration in the group treated with CRH was also observed. For CRH-A, all analysed effects were opposite to those induced by CRH. The study demonstrates that intracerebroventricular (i.c.v.) infusion of both CRH and CRH-A affects the GnRH/GnRHR biosynthesis and LH secretion in follicular-phase sheep conceivably via either central and peripheral mechanisms including Kiss1 neurons activity and cortisol signals. It has also been suggested that CRH and CRH-A infusion probably had effects directly at the AP.

The comparison of microdose flare up and flexible antagonist protocols in poor responders undergoing IVF treatment: A prospective randomized controlled trial

Aim: Ovarian reserve is one of the most important prognostic factors to predict probability of pregnancy in in vitro fertilization (IVF) cycles. Poor ovarian response is associated with high cycle cancellation rate and diminished pregnancy rates. Therefore, the management of women who demonstrate an inadequate response to controlled ovarian hyperstimulation (COH) are a challenge to treat with IVF. Methods: A hundred consecutive infertile women, defined as poor responder, were recruited to this study. It was conducted at the assisted reproductive technology (ART) unit of the Ankara Etlik Zubeyde Hanim Women's Health Teaching and Research Hospital during the period September 2009 to September 2011. All patients in Group 1(n=50) were treated by using flexible gonadotropin releasing hormone (GNRH) antagonist protocol and in Group 2 (n=50) were treated by using GnRH microdose flare-up protocol. Exogenous gonadotropin (Gonal F, Serono, Istanbul, Turkey) was initiated on the second day of menstruation in all patients in Group 1(n=50) and GnRH antagonist (0.25 mg, Cetrotide; Serono, Geneva, Switzerland) was started when the leading follicle reached 12 mm in mean diameter and were continued until the day of hCG administration. Results: Total dosage of gonadotropins was significantly higher in group 2 (2625 IU in group 1 vs 4050 IU in group 2; p&lt;0.001). The pregnancy rate was higher in group 2 but not statistically significant (25.7% in group 1 vs 33.3% in group 2; p=0.501).Conclusion: There is no consensus on the best standard treatment option for assisted reproductive technology (ART) cycles of poor responders. GnRH antagonist and microdose flare-up protocols seem to have similar outcomes in poor responder patients in intracytoplasmic sperm injection (ICSI) cycles except consumption of gonadotropins. Further prospective randomized trials with large sample size are needed to assess the efficacy of the two protocols in the poor responders.

GnRH antagonist for endometrial priming in an oocyte donation programme: a prospective, randomized controlled trial.

Can gonadotrophin releasing hormone (GnRH) antagonist be used in egg donation recipients with ovulatory cycles for the purpose of achieving synchronization between the donor´s and recipient´s cycle? Prospective randomized controlled trial to compare 7-day dosage of GnRH antagonist for endometrial priming in an oocyte donation programme with a single dose of long-acting GnRH agonist. A total of 563 women were randomized in a private single centre, and 473 women underwent embryo transfer. Ongoing pregnancy rate was the primary end point. Analysis was adjusted for embryonic stage at the time of embryo transfer; data collected included days on the waiting list; number of fresh-vitrified oocytes collected; and oocyte donor´s age at the time ofretrieval. No statistically significant differences were found between groups in per intention-to-treat analysis: adjusted OR 1.42 (CI 0.97 to 2.09); per treatment received: adjusted OR 1.43 (CI 0.97 to 2.09); per embryo transfer: adjusted OR for ongoing pregnancy rate 1.47 (CI 1.01 to 2.13), P = 0.047. For women with ovulatory cycles undergoing oocyte donation, the outcomes are similar between GnRH antagonist and down-regulated hormonereplacementprotocols.

A change from gonadotropin releasing hormone antagonist to gonadotropin releasing hormone agonist therapy does not affect the oncological outcomes in hormone sensitive prostate cancer

BackgroundThe aim of our retrospective study was to evaluate the 5-year survival and time to castration resistant prostate cancer in patients with hormone sensitive prostate cancer treated with the gonadotropin releasing hormone antagonist, degarelix. Another aim was to evaluate the effects of changing the treatment from degarelix to a gonadotropin releasing hormone agonist after achieving stable disease control, on the clinical and oncological outcomes.ResultsOur analysis was based on the data of 108 patients with prostate cancer who were treated with degarelix. Of these, the treatment was changed from degarelix to a gonadotropin releasing hormone agonist in 57 patients (changed group), and the treatment with degarelix was continued in the other 51 (continued group). The overall 5-year survival was statistically superior in the changed (96.6%) group than that in the continued (74.1%) group (p = 0.006). The 5-year cancer-specific survival was also superior in the changed (100%) group than that in the continued (84.6%) group (p = 0.027). The average time to castration resistant prostate cancer was comparable in both the changed (43.3 months) and continued (35.2 months) groups (p = 0.117). Lower serum levels of prostate specific antigen and alkaline phosphatase were maintained after changing the therapy from degarelix to a gonadotropin releasing hormone agonist.ConclusionsDegarelix is effective in the treatment of prostate cancer. Degarelix therapy can also be safely changed to a gonadotropin releasing hormone agonist without any adverse clinical or oncological effects.

The Effects of Chemical Castration with Degarelix on Bone Turnover: Densitometric and Biomechanics Bone Properties of Male Rats.

BackgroundGonadotropin releasing hormone (GnRH) antagonists may cause chemical castration in males by suppressing the pituitary-gonadal axis, hence reducing testosterone level. There are limited data on the effects of degarelix, a newer series of potent and long acting GnRH antagonist on bone.ObjectivesThe current study aimed at determining the effects of degarelix on bone turnover, bone densitometry, and bone mechanical strength in male rats.MethodsEighteen male Sprague-Dawley rats were randomly divided into sham (SHAM), orchidectomized (ORX), and degarelix-induced (DGX) groups. Chemical castration was performed by subcutaneous degarelix injection (2 mg/kg) at the scapular region. The rats were scanned for baseline bone mineral area (BMA), bone mineral content (BMC), and bone mineral density (BMD) using dual-energy x-ray absorptiometry (DXA). Following six weeks of experimental period, BMA, BMC, and BMD were measured again with DXA and blood was collected for testosterone and bone biomarkers (osteocalcin and C-terminal of type I collagen crosslink (CTX-1)) measurements. The rats were euthanized and femora were dissected for bone biomechanical strength analysis.ResultsBilateral orchidectomy and degarelix administration significantly lowered serum testosterone level, decreased whole body BMC, femoral BMA, femoral BMC, and femoral BMD (P < 0.05) compared with the SHAM group. However, no significant changes were observed in bone biochemical markers and bone mechanical strength in all experimental groups.ConclusionsIn conclusion, degarelix administration had comparable effects on bone as bilateral orchidectomy. Administration of degarelix provides an alternative method of inducing testosterone deficient-osteopenia in male rats without need for removing the testes.

Delivery of Peptidic Gonadotropin Releasing Hormone Antagonists.

GnRH antagonists have several clinical applications in prostate cancer, regulation of ovulation induction in females, breast cancer, male contraception and others. Antagonists differ from natural GnRH decapeptide in having five or more amino acid substitutions, whereas most of the antagonists are available as subcutaneous (SC) formula for injection some are formulated as a depot formulation for sustained release (e.g., Cetrorelix, Degarelix). Systemic delivery of cetrorelix acetate by intratracheal route can be achieved using dry powder for inhalation of the adhesive mixture when the powder deposition reaches stage four. The oral route for systemic delivery of peptide without its degradation can be achieved using gastrointestinal permeation enhancement technology GIPET® provided by acyline.

Complex chromosomal aberrations in a fetus originating from oocytes with smooth endoplasmic reticulum (SER) aggregates

ABSTRACTThe presence of smooth endoplasmic reticulum aggregates (SERa) in the ooplasm is considered as the most severe oocyte dysmorphism due to its serious and potentially lethal outcomes in offspring. In the present case report, a couple underwent their first intracytoplasmic sperm injection (ICSI) cycle using a gonadotrophin releasing hormone (GnRH) antagonist protocol, followed by fetal ultrasound scanning and amniocentesis. SERa were observed in all oocytes retrieved. A singleton pregnancy was established. The second trimester fetal ultrasound scan revealed a female fetus with overlapping fingers in both hands, and amniocentesis was performed for the detection of chromosomal abnormalities. Comprehensive genetic analysis with the combined use of array-comparative genomic hybridization (CGH), fluoresence in situ hybridization (FISH) and conventional cytogenetics revealed a complex chromosome rearrangement (CCR) involving three break points on two chromosomes, resulting in a reciprocal translocation with a cryptic 2q31 deletion. A week following amniocentesis, there was rupture of amniotic membranes and a stillborn was delivered. This is the first case in the literature to report a CCR with concomitant 2q31 deletion resulting in a well-defined and clinically recognizable contiguous gene syndrome with an abnormal phenotype in a fetus arising from a cohort of oocytes affected by SERa. It is suggested that fertilization and transfer of oocytes with SERa should be avoided, until further research establishes whether there is a causal relationship between the presence of SERa and chromosomal abnormalities in the resulting fetus.Abbreviations: SER: smooth endoplasmic reticulum; ICSI: intracytoplasmic sperm injection; GnRH: gonadotrophin releasing hormone; CGH: comparative genomic hybridization; FISH: fluoresence in situ hybridization; FSH: follicle stimulating hormone; hCG: human chorionic gonadotrophin; OHSS: ovarian hyperstimulation syndrome; IVF: in vitro fertilization; MII: metaphase II; GV: germinal vesicle; CCR: complex chromosome rearrangement

Treatment pathways of Japanese prostate cancer patients - A retrospective transition analysis with administrative data.

BackgroundLimited availability of real-world data that describe treatment patterns of Japanese prostate cancer (PCA) patients.MethodsA biweekly transition analysis of PCA treatment was performed for patients with PCA diagnosis and a specific treatment between 2010 and 2015. To account for different cancer stages, two patient populations were analyzed. The first group consisted of patients on medication for hormone-sensitive prostate cancer (HSPC). The second group is comprised of patients who ended up receiving specific therapy for castration-resistant prostate cancer (CRPC). For each treatment, the average of treatment duration and the portion of patients transitioning to a consecutive treatment was calculated.ResultsWe identified 59,626 patients from the Japanese administrative database with a PCA diagnosis and specific treatment. In the first year of our observational study 786 patients commenced a HSPC treatment and 695 received a CRPC specific therapy Among the HSPC group, we found that combination hormonal therapy, comprised of a gonadotrophin releasing hormone agonist or antagonist with an antiandrogen was more common than monotherapy. The results of the CRPC group indicated that chemotherapy administration was for a shorter time period in a real-world setting as compared to published clinical studies.ConclusionUtilizing a novel method to visualize real-world treatment pathways for PCA patients we found that real treatment pathways are in line with international guidelines.

Clomiphene citrate in LH surge suppression for women undergoing ICSI

Abstract Objective To evaluate the effect of adding clomiphene citrate (CC) in the mid-to-late follicular phase as an adjuvant to gonadotropins to suppress luteinizing hormone (LH) surge in women undergoing intracytoplasmic sperm injection (ICSI). Methods Prospective non-randomized study of 108 women undergoing ICSI and subjected to ovarian stimulation with gonadotropins with addition of CC (50 mg 3 times per day) when a leading follicle reached 14 mm in diameter and continued till the day of human chorionic gonadotropin (HCG) administration. Women subjected to controlled ovarian stimulation (COS) with the gonadotropin-CC protocol (n = 50) were compared with a group of women were to COS with the flexible gonadotropin releasing hormone antagonist (GnRH-ant) protocol (n = 58). Results Serum LH level on day HCG administration was significantly higher in CC group than in GnRH-ant group and the incidence of LH surge was higher in CC group than in GnRH-ant group (10% vs 3.4%, respectively) but without statistically significant difference (P = .246). The oocyte maturation and fertilization rates, the biochemical and clinical pregnancy rates, the implantation rate and the ongoing pregnancy rate were comparable in both groups. Conclusion Adding CC in the mid-to-late follicular phase as an adjuvant to gonadotropins represents a less costly COS which is effective in eliminating the occurrence of premature LH surge without compromising the cycle outcomes in women undergoing ICSI.

High luteinizing hormone weakens urinary continence mechanisms in association with prostaglandin E2 elevation in a postmenopausal rat model.

To explore the role of luteinizing hormone (LH) in the urinary continence mechanism, urethral function was investigated using a postmenopausal rat model with high serum LH concentrations and the postmenopausal rat model given a gonadotropin releasing hormone (GnRH) antagonist to lower LH concentrations. Adult female rats were divided into: 1) sham group; 2) ovariectomy group (OVX) with removal of bilateral ovaries; 3) OVX and GnRH-antagonist administered group (OVX + G); and 4) sham and GnRH-antagonist administered group (Sham + G). Urethral function was evaluated by the sneeze-induced urethral continence reflex experiment, and serum LH and prostaglandin E2 (PGE2) concentrations were measured. In the sneeze-induced urethral continence reflex experiment, urethral baseline pressure (UBP) and the amplitude of the urethral response during sneezing (A-URS) were measured. The UBP was significantly decreased in the OVX group than in the other groups. A-URS was significantly lower in the OVX group than in the Sham group, but with no significant difference compared with the OVX + G group. Lowering the serum LH by a GnRH-antagonist improved UBP to the same level as in the Sham group. The serum PGE2 concentration was significantly higher in the OVX group than in the other groups. The results suggested that the increased serum LH concentration in the OVX rat model worsened the continence mechanism. This mechanism is probably associated with an increased PGE2 concentration, because PGE2 caused urethral smooth muscle relaxation. A GnRH-antagonist might improve urinary incontinence by decreasing the serum LH and PGE2 concentrations.

Suppression of luteinizing hormone enhances HSC recovery after hematopoietic injury.

There is a substantial unmet clinical need for new strategies to protect the hematopoietic stem cell (HSC) pool and regenerate hematopoiesis after radiation injury from either cancer therapy or accidental exposure. Increasing evidence suggests that sex hormones, beyond their role in promoting sexual dimorphism, regulate HSC self-renewal, differentiation, and proliferation. We and others have previously reported that sex-steroid ablation promotes bone marrow (BM) lymphopoiesis and HSC recovery in aged and immunodepleted mice. Here we found that a luteinizing hormone (LH)-releasing hormone antagonist (LHRH-Ant), currently in wide clinical use for sex-steroid inhibition, promoted hematopoietic recovery and mouse survival when administered 24 h after an otherwise-lethal dose of total-body irradiation (L-TBI). Unexpectedly, this protective effect was independent of sex steroids and instead relied on suppression of LH levels. Human and mouse long-term self-renewing HSCs (LT-HSCs) expressed high levels of the LH/choriogonadotropin receptor (LHCGR) and expanded ex vivo when stimulated with LH. In contrast, the suppression of LH after L-TBI inhibited entry of HSCs into the cell cycle, thus promoting HSC quiescence and protecting the cells from exhaustion. These findings reveal a role of LH in regulating HSC function and offer a new therapeutic approach for hematopoietic regeneration after hematopoietic injury.

Studija efikasnosti klomifen citrata u poređenju sa GnRH antagonistima u prevenciji skoka LH među pacijentkinjama koje su na stimulaciji jajnika u procesu IVF-ICSI

Abstract: Objective: To determine the efficacy of clomiphene citrate (CC) in preventing luteinizing hormone (LH) surge without adding gonadotropin releasing hormone (GnRH) antagonist or GnRH agonist in stimulated first fresh intracytoplasmic sperm injection cycle by evaluating the outcome of oocytes and embryo quality. Design: Registry cohort study. Settings: Fertility Clinic Registry at Hospital University Kebangsaan Malaysia. Patients: A total of 235 fresh stimulated ICSI cycle for patients aged 18-40 years old using clomiphene citrate plus gonadotropin (n = 117) and GnRH antagonist plus gonadotropin (n = 118) were studied. Intervention: Comparing two different ovarian stimulation protocol. Main outcome measure(s): Social economical demographic, ovarian stimulation response and laboratory outcome. Fertilization rate as our primary outcome and our secondary outcome were oocyte retrieval rate, mature oocyte rate and top quality embryo rate. Result(s):There were no difference in the demographic and hormonal characteristic of the study groups. The primary outcome of fertilization rate has significant difference with p value of 0.003; 73.2% for CC group and 64.2% for GnRH antagonist group. The secondary outcome of OR rate (78.4% ± 17.6% VS 80.3% ± 13.4%, p = 0.368), mature oocyte rate (85.2% ± 19.0 VS 81.7% ± 16.7%, p = 0.130) and top quality embryo rate (79.4% ± 24.2% VS 74.9% ± 22.9%, p = 0.178) were comparable between both groups. There were significant difference between the endometrial thickness on the day of trigger and OHSS risk among both groups (8.5 mm ± 1.0 mm VS 9.4 mm ± 1.1 mm, p &lt; 0.001 and 12.8% VS 44.1% respectively). Discussion: Minimal stimulation protocol with CC and gonadotropin may be the answer to many infertile couples in need of IVF and yet having financial situation deterring them in attempting IVF treatment. GnRH antagonist could be safely replaced by CC by extending to 10 days as this protocol gives better primary outcome and comparable secondary outcomes with less OHSS. CC is recognized to induce thinning of endometrial lining and thus, may impair embryo implantation. However, with advancement of the vitrification system and higher success rate in frozen-thaw embryo transfer worldwide provides an excellent solution for this issue.