Boosting cognition with a hormone.

A hormone enhances cognition in mouse models of Alzheimer's disease and Down syndrome.

Effect of GnRH agonist alone or combined with different low-dose hCG on cumulative live birth rate for high responders in GnRH antagonist cycles: a retrospective study.

BACKGROUND: There is insufficient evidence regarding the impact of dual trigger on oocyte maturity and reproductive outcomes in high responders. Thus, we aimed to explore the effect of gonadotropin-releasing hormone agonist (GnRHa) trigger alone or combined with different low-dose human chorionic gonadotropin (hCG) regimens on rates of oocyte maturation and cumulative live birth in high responders who underwent a freeze-all strategy in GnRH antagonist cycles. METHODS: A total of 1343 cycles were divided into three groups according to different trigger protocols: group A received GnRHa 0.2 mg (n = 577), group B received GnRHa 0.2 mg and hCG 1000 IU (n = 403), and group C received GnRHa 0.2 mg and hCG 2000 IU (n = 363). RESULTS: There were no significant differences in age, body mass index, and rates of oocyte maturation, fertilization, available embryo, and top-quality embryo among the groups. However, the incidence of moderate to severe ovarian hyperstimulation syndrome (OHSS) was significantly different among the three groups (0% in group A, 1.49% in group B, and 1.38% in group C). For the first frozen embryo transfer (FET) cycle, there were no significant differences in the number of transferred embryos and rates of implantation, clinical pregnancy, live birth, and early miscarriage among the three groups. Additionally, the cumulative ongoing pregnancy rate and cumulative live birth rate were not significantly different among the three groups. Similarly, there were no significant differences in gestational age, birth weight, birth height, and the proportion of low birth weight among subgroups stratified by singleton or twin. CONCLUSIONS: GnRHa trigger combined with low-dose hCG (1000 IU or 2000 IU) did not improve oocyte maturity and embryo quality and was still associated with an increased risk of moderate to severe OHSS. Therefore, for high responders treated with the freeze-all strategy, the single GnRHa trigger is recommended for final oocyte maturation, which can prevent the occurrence of moderate to severe OHSS and obtain satisfactory pregnancy and neonatal outcomes in subsequent FET cycles.

The GnRH Antagonist Degarelix Suppresses Gonadotropin Secretion and Pituitary Sensitivity in Midgestation Sheep Fetuses.

The specific role of gonadotropin-releasing hormone (GnRH) on brain sexual differentiation remains unclear. To investigate whether gonadotropin and, in turn, testosterone (T) secretion is regulated by GnRH during the critical period for brain differentiation in sheep fetuses, we attempted to selectively suppress pituitary-testicular activation during midgestation with the long-acting GnRH antagonist degarelix. Fetuses received subcutaneous injections of the antagonist or vehicle on day 62 of gestation. After 2 to 3 weeks we examined consequences of the intervention on baseline and GnRH-stimulated plasma luteinizing hormone (LH) and T levels. In addition, we measured the effect of degarelix-treatment on messenger RNA (mRNA) expression for the pituitary gonadotropins and key gonadal steroidogenic enzymes. Baseline and GnRH-stimulated plasma LH levels were significantly suppressed in degarelix-treated male and female fetuses compared to control values. Similarly, T concentrations were suppressed in degarelix-treated males. The percentage of LHß-immunoreactive cells colocalizing c-fos was significantly reduced by degarelix treatment indicating that pituitary sensitivity was inhibited. Degarelix treatment also led to the significant suppression of mRNA expression coding for the pituitary gonadotropin subunits and for the gonadal enzymes involved in androgen synthesis. These findings demonstrate that pharmacologic inhibition of GnRH early in gestation results in suppression of LH secretion and deficits in the plasma T levels of male lamb fetuses. We conclude that GnRH signaling plays a pivotal role for regulating T exposure during the critical period of sheep gestation when the brain is masculinized. Thus, disturbance to gonadotropin secretion during this phase of gestation could have long-term consequence on adult sexual behaviors and fertility.

Improved reproductive performance achieved in tropical dairy cows by dietary beta-carotene supplementation.

Dairy farming in tropical climates is challenging as heat stress can impair reproduction in cows. Previous studies have demonstrated the beneficial effects of beta-carotene supplementation on bovine reproductive performance. This study was performed in Thailand, where the temperature-humidity index (THI) during the experimental periods was measured to range from 78.4 to 86.1. Lactating Holstein cows classified as repeat breeders (previous artificial insemination [AI] failures) were randomly assigned into two treatments, control treatment (T1; received placebo, n = 200) and test treatment (T2; received 400 mg/h/day of beta-carotene, n = 200). All cows were subjected to a protocol for synchronization of ovulation and timed artificial insemination (TAI). The day of the 1st ovulation synchronized protocol was defined as day 0, and the total experimental period was 160 days. Daily placebo or beta-carotene supplements were given orally on day 0 and each subsequent day of the experiment. Diagnosis of pregnancy was performed using ultrasound on day 30 after insemination. Non-pregnant cows were subjected to further ovulation synchronizations (maximum of four) and TAI over a period of 160 days. Milk samples were collected every ten days throughout the experiment. The samples were analyzed for beta-carotene concentration, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. The pregnancies per AI of the cows in T2 were significantly greater than that of T1 from the 2nd to 4th TAI. During the entire experimental period, the pregnancies in T2 were significantly greater than that of T1. Cox's proportional hazards regression model data indicated a 44% greater probability of pregnancy for cows receiving beta-carotene. The concentrations of milk beta-carotene in T2 were significantly greater than T1 from the 2nd to 4th TAI. Significantly greater SOD and GPx activities were observed in T2 than T1, suggesting a reduction of oxidative stress in cows treated with beta-carotene. Dietary supplementation with beta-carotene thus improves the reproductive performance of repeat breeders exposed to heat stress, possibly by reducing oxidative stress.

Comparison of efficacy of Ovsynch protocol to single PGF2α administration in treatment of individual dairy cows with post-service subestrus.

The aim of this study was to evaluate the efficacy of the Ovsynch protocol in the treatment of post-service subestrus in individual dairy cows compared to a single administration of PGF2α. The study was performed on 517 Polish Friesian Holstein cows with post-service anestrus over four years in 3 dairy herds under a herd health program. Cows (n=240) diagnosed ultrasonographically as non-pregnant and with a mature corpus were treated with a single PGF2α administration and inseminated at detected estrus. Cows without corpus (n=277) were treated with the Ovsynch protocol. The estrus detection rate after PGF2α administration, percentages of cows pregnant after the treatment and at day 260, intervals from parturition to treatment and from treatment to conception and pregnancy loss rates were calculated. The overall percentage of cows pregnant after treatment did not differ between animals treated with the Ovsynch protocol and with PGF2α (38.9% vs. 42.5%; p>0.05). In herd A the percentage of cows pregnant after treatment was significantly lower (p⟨0.05) for the Ovsynch group than for the PGF2α group (30.2% vs. 61.2%). In contrast, in herd C the percentage of cows pregnant after treatment was significantly higher (p⟨0.05) in the Ovsych group than in the PGF2α group (39.6% vs. 28.8%). The overall estrus detection rate after administration of PGF2α was 59.6%. However, it was significantly lower (p⟨0.05) in herd C (44.7%) than in herds A (79.6%) and B (76.3%). The overall pregnancy loss rate ranged from 5.1% to 13.3% and did not differ significantly between herds and treatment groups (p>0.05). In conclusion, Ovsynch protocol can be a useful alternative for treatment of post-service suboestrus in individual cows in dairy herds with insufficient oestrus detection.

GnRH Antagonist Protocol With Cessation of Cetrorelix on Trigger Day Improves Embryological Outcomes for Patients With Sufficient Ovarian Reserve.

Objective: To evaluate the efficiency and validity of cessation of cetrorelix on trigger day during gonadotropin releasing hormone antagonist (GnRH-ant)-controlled ovarian stimulation of in vitro fertilization (IVF) cycles. Methods: In this retrospective study, a total of 1271 patients undergoing initial IVF cycles following the GnRH-ant protocol were enrolled; 832 patients received cetrorelix on trigger day (Group A) and 439 patients ceased cetrorelix on trigger day (Group B). We compared demographic characteristics, embryological and clinical outcomes between the two groups. A Poisson regression model was used to identify factors that significantly affected embryological outcomes. Patients were further divided into subgroups according to anti-Mullerian hormone (AMH) and age, to assess associations between ceasing cetrorelix on trigger day and embryological outcomes. Results: There was a significant improvement on embryological outcomes in patients who ceased cetrorelix on trigger day, and there were no significant differences in clinical outcomes or preovulation rates between the two groups. Furthermore, for patients with 1.1 ≤ AMH ≤ 4.7 ng/ml, all embryological outcomes were significantly higher in Group B compared with Group A. For patients with AMH > 4.7 ng/ml, the number of oocytes retrieved, fertilization rate (2PN) of IVF cycles and proportion of day 3 good quality embryos were all significantly higher in Group B. For patients with age < 35 years, all the embryological outcomes, besides the number of available embryos, were significantly higher in Group B than in Group A. There were no differences in embryological outcomes between the two groups when patients were stratified based on age > 35 years or AMH < 1.1 ng/ml. Conclusion: GnRH-ant protocol with cessation of cetrorelix on trigger day improved embryological outcomes for young patients or patients with sufficient ovarian reserve, and was effective at preventing preovulation.

Effects of half-dose and full-dose GnRH antagonists on IVF-ET outcomes: a retrospective study.

BACKGROUND: Gonadotropin-releasing hormone antagonist(GnRH-ant) has been shown to have a negative effect on endometrial receptivity. Therefore, the use of lower doses of GnRH-ant during controlled ovarian stimulation (COS) may improve endometrial receptivity and clinical pregnancy rate. However, the GnRH-ant dose is relatively flexible and there is no fixed requirement for guidance. In this retrospective study, we determined the effects of half-dose and full-dose GnRH-ant on IVF-ET outcomes. METHODS: Of the 316 cycles in the 314 patients analyzed in this study, 149 received GnRH-ant half-dose (Group1), while 167 received GnRH-ant full-dose (Group2). The groups were further classified based on age and BMI. Age subgroups, were divided as age ≤ 35(subgroup A) and age > 35(subgroup B): 180 cycles in subgroup A (107 cycles in subgroup A1,73 cycles in subgroup A2), 136 cycles in subgroup B (42 cycles in subgroup B1,94 cycles in subgroupB2). The subgroups based on BMI were divided as BMI < 25 (subgroup C)and BMI ≥ 25 (subgroup D):208 cycles in subgroup C (94 cycles in subgroup C1,114 cycles in subgroup C2), 108 cycles in subgroup D (55 cycles in subgroup D1,53 cycles in subgroup D2). RESULTS: The number of fertilized oocytes, superior-quality embryos, clinical pregnancy rate, and live birth rate differed significantly between the two groups. However, the number of retrieved oocytes and available embryos were significantly higher in Group 1 than Group 2 (8.17 ± 4.10 vs. 7.07 ± 4.05, 2.96 ± 2.03 vs. 2.52 ± 1.62, respectively,p<0.05). Differences between the age subgroups were not statistically significant. However, in the subgroups based on BMI, the fertilized oocytes, available embryos, the number of superior-quality embryos, and the live birth rate differed significantly between the four subgroups. The number of retrieved oocytes was higher in subgroup C1 than in subgroup C2 (8.24 ± 4.04 vs. 6.83 ± 3.92,p < 0.05), In addition, the clinical pregnancy rate was slightly higher in subgroup D1 than in subgroup D2(45.45 vs. 24.53%, P < 0.05). CONCLUSIONS: The results showed that half-dose GnRH-ant was as effective as full-dose GnRH-ant for most patients. Moreover, half-dose GnRH-ant may be more suitable in patients with BMI greater than or equal to 25. The findings of this study need to be validated in a large sample RCT. TRIAL REGISTRATION: Retrospectively registered.

A Novel Promising Endometrial Preparation Protocol for Frozen-Thawed Embryo Transfer: A Randomized Controlled Trial.

Background: In recent years frozen-thawed embryo transfer (FET) has played an increasingly important role in ART, but there is limited consensus on the most effective method of endometrial preparation (EP) for FET. Inspired by significantly higher implantation rate and clinical pregnancy rate of the depot GnRH-a protocol, we proposed a novel EP protocol named down-regulation ovulation-induction (DROI) aimed to improve pregnancy outcomes of FET. Methods: This was a single-center, randomized controlled pilot trial. A total of 307 patients with freeze-all strategy scheduled for first FET were enrolled in the study. A total 261 embryos were transferred in DROI-FET group including 156 patients and 266 embryos were transferred in mNC-FET group including 151 patients. Reproductive outcomes were compared between the two groups. Results: The basic characteristics of patients, and the average number, quality and stage of embryos transferred were comparable between the two groups. Our primary outcome, implantation rate(IR) in DROI-FET group, was significantly higher than that of the mNC-FET group (54.41% versus 35.71%, P<0.01). The clinical pregnancy rate (CPR) and ongoing pregnancy rate (OPR) in DROI-FET group was also higher than that in mNC-FET group (69.87% versus 50.33%, P<0.01; 64.10% versus 42.38%, P<0.01). Conclusions: Compared to existing endometrial preparation methods, the DROI protocol might be the more efficient and promising protocol.

Double daily doses of cetrorelix may raise follicular phase progesterone more compared to single doses in poor ovarian response patients.

PURPOSE: There is evidence that follicular phase progesterone rise [FPPR] adversely affects fresh in vitro fertilization [IVF] cycles. A single daily dose of cetrorelix has been used to prevent early luteinizing Hormone (LH) surge. We speculated that doubling the daily dose might have a positive effect in patients who have early LH surges despite receiving the single daily dose treatment. However, a double daily dose of cetrorelix seems to cause FPPR in poor ovarian response (POR) patients. MATERIALS AND METHODS: On human chorionic gonadotropin [hCG] injection days, the progesterone levels of POR patients who received a single daily dose of cetrorelix (group 1, n = 59) were compared with progesterone levels of the patients who received a double daily dose of cetrorelix (group 2, n = 75). The two groups had statistically similar demographic data. The patients who had FPPR were detected, and a comparison of progesterone levels, using 0.8, 1.0, and 1.2 [ng/mL] of progesterone as cut-off levels, was made between patients of both groups. RESULTS: FPPR patients in group 2 had significantly higher progesterone levels during hCG day, contrary to expectations. When progesterone cut-off levels of 0.8, 1.0, and 1.2 [ng/mL] were used for group 1 patients, 15.3%, 13.6%, and 6.8% of the patients developed FPPR, respectively When the progesterone cut-off levels of 0.8, 1.0, and 1.2 [ng/mL] were used for group 2, the results detected were 45.3%, 30.7%, and 21.3%, respectively. A significant statistical difference in progesterone levels was observed between the groups. CONCLUSION: While the double daily dose of cetrorelix was initially thought to more effectively suppress early LH rise by some authors, we have seen that it increases the FPPR more when compared to a single daily dose regime. We suggest using frozen cycles instead of fresh cycles in order to have better endometrial receptivity in patients who seem to benefit from higher daily doses of cetrorelix.

The effect of GnRH stimulation on AMH regulation in central precocious puberty and isolated premature thelarche.

OBJECTIVES: There is a complex interaction between the anti-müllerian hormone (AMH) and hypothalamic-pituitary-gonadal axis. However, the effect of gonadotropin-releasing hormone (GnRH) stimulation on AMH levels is not clearly known. In the study, we aimed to evaluate the effect of GnRH stimulation on AMH levels in central precocious puberty (CPP) and isolated premature thelarche (PT) groups. METHODS: Sixty-three girls with breast development before the age of 8 were enrolled in the study. GnRH test was performed on all subjects. Blood samples for follicle-stimulating hormone (FSH), luteinizing hormone (LH), and AMH levels were taken at basal, 40th, and 90th minute of GnRH test. Subjects were grouped as CPP and PT group. RESULTS: After GnRH stimulation, AMH levels increased significantly at the 40th minute and the stimulating effect of GnRH on AMH continued till the 90th minute (p: 0.0001). There was a positive correlation between basal and 90th-minute AMH levels (r: 479, p: 0.0001). The highest FSH, LH, and AMH times were significantly different after the GnRH stimulation (p: 0.001, p: 0.001, and p: 0.007). Although the CPP group had a lower basal AMH level than the PT group's basal AMH level; AMH response to GnRH stimulation was not different (p>0.05). CONCLUSIONS: In our study, which examined the effect of GnRH stimulation on AMH levels in early pubertal development disorders for the first time, GnRH stimulated AMH secretion rapidly, correlated with basal AMH. Basal AMH levels were lower in patients with CPP than in those with PT; however, the effect of GnRH stimulation on AMH levels was similar in both groups.

Optimizing pediatric histrelin implantation to improve success rates in clinic without sedation.

OBJECTIVES: The purpose of this study was to review our success rate performing the histrelin implant procedure in clinic without sedation. METHODS: A retrospective study was performed for histrelin implant procedures done at our institution from 2008 to 2020. Wilcoxon rank-sum test or Fisher's exact test was utilized to identify significant differences (p<0.05). RESULTS: A total of 73 patients underwent 184 histrelin implant procedures from 2008 to 2020. In the past few years, there has been a decrease in procedures for precocious puberty and an increase for gender dysphoria. The majority of procedures were performed in clinic without sedation (82%). The only risk factor associated with requiring sedation was younger age (median 9 vs. 10 years; p<0.003). Complications (i.e. implant fracture or need for counter-incision) were noted in 10 of the procedures (5%). The only risk factor identified for a procedural complication during implant removal/replacement was interval time from insertion (21 vs. 13 months; p<0.01). The only documented wound problem reported was dermatitis in 1 patient (no suture granuloma, dehiscence, or implant extravasation). CONCLUSIONS: Procedural refinements and distraction therapy have enabled us to perform the majority of procedures in clinic without sedation. In our experience, procedural difficulty and complications appear to increase with prolonged implant duration. Histrelin implantation is increasingly being performed for gender dysphoria.

Effects of GnRHa and hCG with or without dopamine receptor antagonists on the spawning efficiency of African catfish (Clarias gariepinus) reared in hatchery conditions.

Optimization of artificial reproduction is essential for minimizing genetic diversity, especially when fish are captured from their natural habitats and spawned in controlled conditions. In the present study, there was evaluation of the effects of gonadotropin-releasing hormone analogue (GnRHa) and human chorionic gonadotropin (hCG) with or without dopamine receptor antagonists such as domperidone (DOM) and metoclopramide (MET) on the spawning efficiency of African catfish (Clarias gariepinus) reared in captivity. The control group was intramuscularly (IM) injected with 1 mL of sterile saline solution. The fish specimens of the other six groups were injected IM with GnRHa or hCG, or in combination with either DOM or MET. None of the specimens had ovulations in the control group. There was the longest latency period in specimens treated with only GnRHa or hCG. There were the largest egg mass weight, fecundity, and hatchability (%) in specimens of the GnRHa + MET group. These findings indicate that GnRHa or hCG combined with dopamine receptor antagonists such as DOM and MET resulted in a marked enhancement of ovulation rate and increased the egg mass, fecundity, and hatchability of the treated C. gariepinus, and the values when there was inclusion of the MET treatment exceeded those when there was treatment with DOM.

Clinical characteristics and treatment patterns with histrelin acetate subcutaneous implants vs. leuprolide injections in children with precocious puberty: a real-world study using a US claims database.

OBJECTIVES: Gonadotropin-releasing hormone analogs are the treatment of choice for central precocious puberty (CPP). This study characterizes patients treated with histrelin implant or leuprolide injection. METHODS: A US claims database was used to identify patients aged ≤20 years with ≥1 histrelin or leuprolide claim (index treatment) between April 2010 and November 2017 and continuous enrollment ≥3 months before and ≥12 months after the index treatment date. RESULTS: Overall, 4,217 patients (histrelin, n=1,001; leuprolide, n=3,216) were identified. The percentage of patients with CPP diagnosis was greater in the histrelin (96.5%) vs. leuprolide (68.8%; p<0.0001) cohort. In patients with CPP (histrelin, n=966; leuprolide, n=2,214), mean age at treatment initiation was similar for histrelin (9.0 ± 2.0 years) and leuprolide (9.1 ± 2.3 years), with >50% of patients aged 6-9 years. Mean treatment duration was significantly longer for histrelin (26.7 ± 14.8 months) vs. leuprolide (14.1 ± 12.1 months; p<0.0001), and was longer in younger patient groups. More patients switched from leuprolide to histrelin (12.3%) than vice versa (3.6%; p<0.0001). Median annual total treatment costs were slightly lower for the histrelin cohort ($23,071 [interquartile range, $16,833-$31,050]) than the leuprolide cohort ($27,021 [interquartile range, $18,314-$34,995]; p<0.0001). CONCLUSIONS: Patients with CPP treated with histrelin had a longer duration of treatment, lower rates of index treatment discontinuation, and lower annual treatment costs vs. those treated with leuprolide.

Effects of GnRH and hCG administration during early luteal phase on estrous cycle length, expression of estrus and fertility in lactating dairy cows.

Our objective was to determine the effects of a single treatment of human chorionic gonadotropin (hCG) or GnRH from d 5 to 7 of the estrous cycle on cycle length, expression of estrus and fertility in lactating dairy cows. Lactating Holstein cows (n = 354) located in Farm 1 and lactating Jersey cows located in Farm 2 (n = 210) detected in estrus by an Automated Activity Monitor (AAM) system from 27 to 50 days in milk (DIM) were randomly assigned to receive one of three treatments from d 5 to 7 of the estrous cycle: control (untreated; CON; Holstein, n = 111; Jersey, n = 66), GnRH (86 µg gonadorelin acetate im; Holstein, n = 116; Jersey, n = 75), or hCG (3,300 IU im; Holstein, n = 127; Jersey, n = 69). Ovaries were scanned with ultrasound in a random subgroup of cows (Holstein/Farm 1, n = 147; Jersey/Farm 2, n = 94) on the day of treatment and 3 or 4 d later to determine ovulation. Estrus was detected after treatment by an AAM, and peak activity and heat index were recorded. A random subgroup of cows observed in estrus after treatment received first AI from 51 to 80 DIM (Holstein, n = 208; Jersey, n = 138). Pregnancy diagnoses were performed by transrectal ultrasonography at 37 ± 3 d post-AI. Holstein and Jersey cows treated with GnRH and hCG had an increased (P < 0.05) ovulatory response compared with controls. Human chorionic gonadotropin decreased (74%; P = 0.05) and GnRH tended to reduce (75%; P = 0.07) the proportion of multiparous Holstein cows returning to estrus compared with CON (86%). Cows treated with hCG had a longer (P < 0.01) estrous cycle length (24.6 ± 0.3 d, Holstein; 23.0 ± 0.3 d, Jersey) compared with CON cows (22.7 ± 0.3 d, Holstein; 21.3 ± 0.3 d Jersey) and GnRH (22.9 ± 0.3 d, Holstein; 21.1 ± 0.3 d Jersey). The percentage of cows with high (≥80) peak activity and heat index did not differ (P > 0.50) between treatments, and milk production did not affect (P > 0.65) the duration of estrus. Pregnancy per AI (P/AI) was not affected by treatments in Holstein (P = 0.93; CON: 34.3%, GnRH: 35.4%, and hCG: 31.5%) and in multiparous Jersey cows (P = 0.35; CON: 34.3%, GnRH: 35.4%, and hCG: 31.5%), but hCG had greater (P = 0.03; 55%) P/AI than GnRH (30.0%) and a trend (P = 0.06) for greater P/AI than CON (33.3%) in primiparous Jersey cows. In summary, inducing the formation of an accessory corpus luteum from d 5 to 7 of the estrous cycle with hCG reduced expression of estrus in multiparous Holstein cows. Moreover, hCG increased estrous cycle length in Holstein and Jersey cows, and it did not affect first service P/AI at 37 ± 3 d post-AI in Holstein and multiparous Jersey lactating cows. However, hCG increased P/AI in primiparous Jersey cows. Future research with a larger number of cows is needed to confirm these intriguing fertility results.

Fixed versus flexible antagonist protocol in women with predicted high ovarian response except PCOS: a randomized controlled trial.

BACKGROUND: No previous study directly compares the fixed day-5 initiation versus the flexible initiation of GnRH antagonist administration in IVF/ICSI for those patients who are predicted as high ovarian responders without PCOS. To evaluate whether the number of oocytes retrieved is different by using the two GnRH antagonist protocols in Chinese women with predicted high ovarian response except PCOS. METHODS: A randomized controlled trial of 201 infertile women with predicted high ovarian response except PCOS undergoing in vitro fertilization. Ovary stimulation was performed using recombinant FSH and GnRH antagonists. GnRH antagonist ganirelix (0.25 mg/d) was started either on day 5 of stimulation (fixed group) or when LH was > 10 IU/L, and/or a follicle with mean diameter > 12 mm was present, and/or serum E2 was > 600 pg/ml. Patient monitoring was initiated on day 3 of stimulation in flexible group. RESULT(S): No significant difference was observed between the fixed and flexible groups regarding the number of oocytes retrieved (16.72 ± 7.25 vs. 17.47 ± 5.88, P = 0.421), the Gonadotropin treatment duration (9.53 ± 1.07 vs. 9.67 ± 1.03, P = 0.346) and total Gonadotropin dose (1427.75 ± 210.6 vs. 1455.94 ± 243.44, P = 0.381). GnRH antagonist treatment duration in fixed protocol was statistically longer than the flexible protocol (6.57 ± 1.17 vs 6.04 ± 1.03, P = 0.001). There was no premature LH surge in either protocol. CONCLUSION(S): Fixed GnRH antagonist administration on day 5 of stimulation appear to achieve a comparable oocyte retrieved compared with flexible antagonist administration. TRIAL REGISTRATION: NCT02635607 posted on December 16, 2015 in clinicaltrials.gov.

Induction of reproductive activity and egg production by gonadotropin-releasing hormone in non-laying hens.

The current study was conducted to evaluate the effects of gonadotropin-releasing hormone (GnRH) analogue (Receptal) injection on reproductive traits of fully mature layers hens (32 weeks) suffered from inactive ovaries. Ninety-six non-laying hens (TETRA-SL brown egg layers), selected from a commercial flock, with similar body weight, were randomly assigned to four groups (n = 24). Hens in the 1st group served as a control. Hens of the 2nd, 3rd and 4th groups were individually intramuscularly injected every 4 days with 50, 100 and 150 µl of Receptal solution, respectively, for two times. The results stated that the injection of Receptal induced the non-laying hens to produce eggs, but control birds did not produce eggs during the experimental period. The distance between pelvic bones and between the pelvic bone and keel bone of hens was significantly improved (p < .001) in groups received different GnRH levels compared with the control group. The best results were observed in the group injected with 100 µl Receptal. Levels of LH, FSH, oestrogen and progesterone hormones were significantly (p < .05) higher in Receptal-treated groups than in the control group. Hens injected with Receptal had an increase in ovary%, yellow follicles number, oviduct% and oviduct length (p < .001) compared with the control. It was concluded that treating inactive ovaries in non-laying hens with GnRH injections for two times, 4-day intervals, is an effective procedure for inducing egg production and useful in cost reduction in layer farms, and the group treated with 100 µl Receptal had the best results.

The risk of menopausal symptoms in premenopausal breast cancer patients and current pharmacological prevention strategies.

Introduction: For young premenopausal breast cancer (BC) patients, adjuvant chemotherapy and other anti-cancer treatments can increase the risk of menopausal symptoms and may cause chemotherapy-related amenorrhea (CRA), infertility and premature ovarian insufficiency (POI).Areas covered: In this report, menopausal symptoms related to anti-cancer treatment are described. Menstrual disturbances associated with the use of adjuvant chemotherapy, endocrine therapy, and targeted therapy against human epidermal growth factor receptor 2 (HER2) in premenopausal women withBC are discussed. To prevent menopausal symptoms, CRA and POI, data on the efficacy of temporary ovarian suppression with gonadotropin-releasing hormone analogues (GnRHa) during chemotherapy are highlighted. Pooled analyses have confirmed that concurrent administration of GnRHa during chemotherapy could significantly reduce the risk of developing chemotherapy-induced POI in premenopausal women with early-stageBC. In addition, reports have suggested that embryo/oocyte cryopreservation may increase the chance of pregnancy after the diagnosis ofBC, although such data remain limited.Expert opinion: Commonly experienced by pre-menopausal women withBC, anti-cancer treatment could cause severe menopausal symptoms. Temporary ovarian suppression with GnRHa during chemotherapy provided asafe and efficient strategy to reduce the likelihood of chemotherapy-induced POI in premenopausal patients with early-stageBC undergoing (neo)-adjuvant chemotherapy.

LRH-A3 and HCG increase pregnancy rate during timed artificial insemination in dairy cows.

The objective of this study was to use luteinizing hormone-releasing hormone A3 (LRH-A3) and human chorionic gonadotrophin (HCG) to improve pregnancy rate of dairy cows during timed artificial insemination (TAI). In experiment 1, the TAI process (0 d, GnRH, 100 µg; 7 d, PGF2α, 0.4 mg; 56 hr, GnRH, 100 µg; 16 hr, AI) was applied to 160 dairy cows on 50th and 60th days after parturition respectively. In experiment 2, 320 postpartum dairy cows were treated with TAI (Group A), TAI + 25 µg LRH-A3 (Group B), TAI + 1,500 IU HCG 5 days after AI (Group C), and TAI + 25 µg LRH-A3 + 1,500 IU HCG 5 days after AI (Group D). In experiment 3, endometrial cells were treated with HCG. The results showed that TAI did not affect the pregnancy rate, while LRH-A3 and HCG increased the pregnancy rate of the cow. HCG of 5 IU/ml and 10 IU/ml increased the expressions of leukemia inhibitory factor but decreased those of interleukin-6, epidermal growth factor and vascular endothelial growth factor in endometrial cells. This study provided a plan for the use of LRH-A3 and HCG to increase pregnancy rate during TAI in dairy cows.

Effect of tamoxifen with or without gonadotropin-releasing hormone analog on DXA values in women with breast cancer.

The purpose of this study was to compare the changes in DXA values including trabecular bone score (TBS) and bone mineral density (BMD) of lumbar spine (LS) and femur according to the hormone therapies including tamoxifen (TMXF) treatment with or without gonadotropin releasing hormone analog (GnRH analog) in women with breast cancer. We enrolled 119 women with breast cancer who had undergone breast-conserving surgery or mastectomy followed by TMXF treatment for postmenopausal women (TMXF group, n = 63, 52.9%) or by combination therapy of TMXF combined with GnRH analog for premenopausal women (TMXF + GnRH group, n = 56, 47.1%) from December 2013 to December 2017. The median follow-up period was 13 months (interquartile range [IQR], 12.0-14.75) for TMXF group and 13.5 months (IQR, 12.00-16.00) for TMXF + GnRH group, respectively. Patients did not receive bone-modifying therapy. The baseline dual-energy X-ray absorptiometry (DXA) scan before breast cancer surgery and follow-up DXA during hormone therapy. Comparing the first and follow-up DXA results, BMD in LS were significantly decreased in both TMXF (P < 0.001, mean difference: - 0.06) and TMXF + GnRH (P < 0.001, mean difference: - 0.09) groups. BMD values of femoral neck (P = 0.0011, mean difference: - 0.01) and total femur (P < 0.001, mean difference: - 0.03) was significantly changed between the baseline and follow-up DXA in TMXF + RnRH group. In the TMX group, a significant changed occurred in the BMD in total femur (P < 0.001, mean difference: - 0.030) but not the BMD of femoral neck (P = 0.095, mean difference: - 0.007). Regarding TBS, no significant change was found in the TMXF (P = 0.574, mean difference: - 0.004) group, whereas there was a significant decrease in TBS in the TMXF + GnRH (P < 0.001, mean difference: - 0.02) group during follow-up. TBS is more sensitive in reflecting the bone microarchitecture changes by TMXF or GnRH agonist in breast cancer patients than BMD. This finding demonstrates that TBS can be a useful parameter to detect bone microarchitectural changes in clinical applications.

Effect of oral administration of GnRHa+nanoparticles of chitosan in oogenesis acceleration of goldfish Carassius auratus.

Several methods have been used to accelerate previtellogenesis and vitellogenesis stages in fish, including hormonal induction, sustained-release delivery systems, and oral delivery of gonadotropin-releasing hormone (GnRH). In this study, we proposed the oral administration of GnRH analog + nanoparticles of chitosan to accelerate oogenesis in goldfish as a model fish in reproductive biology and aquaculture. In this regard, adult female goldfish were fed with six experimental groups: chitosan, 50 µg GnRHa/kg b.w., 100 µg GnRHa/kg b.w., chitosan + 50 µg GnRHa/kg b.w., and chitosan + 100 µg GnRHa/kg b.w., and diet without any additive as the control for 40 days in triplicate. Every 10 days, ovarian samples were collected, and gonadosomatic index (GSI), oocyte diameter (OD), zona radiata thickness (Zr), and diameter of the follicular layer (Fl) were measured to assess ovarian developmental stage for each treatment. Additionally, blood sampling was done to measure serum 17ß-estradiol concentration at the end of the experiment. All parameters remained unchanged during the experiment in the chitosan-fed group. In the group fed with 100 µg GnRH or chitosan nanoparticle + 100 µg GnRHa, these parameters in general were increased. However, the effects in 50 µg GnRHa or chitosan nanoparticle + 50 µg GnRHa treatments were uncertain; they affected serum E2 levels as a trend toward a significant increase was observed in goldfish treated with chitosan nanoparticle + 100 µg GnRHa. Finally, the results indicated the oral administration of chitosan + 100 µg GnRHa/kg b.w. significantly accelerated the oocyte development and growth of ovary.