Injection Of Gonadotropin-releasing Hormone Agonist Research Articles

Fertility response of anestrous buffaloes to eCG2-Modified or Norgestomet plus eCG6- Modified-GnRH-based ovsync protocols during the breeding season.

Objective: The aim of the current study was to evaluate the fertility response of anestrous buffaloes and associated follicular growth and hormonal profiles to eCG-Modified (eCG2-ovsync) or eCG plus Norgestomet ear implant-Modified (Norgestomet-eCG6-ovsync) GnRH-Based ovsync protocols. Methods: Buffaloes (n=42) were randomly allocated into three treatment protocols: Basic-ovsync, Norgestomet-eCG6-ovsync and eCG2-ovsync (14 each). Each buffalo-cow in the Basic-ovsync protocol received two GnRH agonist injections on Days 0 (GnRHa1) and Day 9 (GnRHa2) and an injection of PGF2α on Day 7 with TAI at 16 h after GnRHa2 injection. Buffaloes in Norgestomet eCG6-ovsync (n=14) received the same treatment as Basic –ovsync plus IM injection of 250 mg of long-lasting progesterone and S/C insertion of Norgestomet ear implant in the ear Conca on Day 0 and an injection of 500 IU eCG on Day 6. Buffaloes in eCG2-ovsync received the same treatment of Basic ovsync in addition to an injection of 1000 IU eCG on Day 2. Simultaneous transrectal ultrasonography (TUS) and blood sampling were performed on Days -10, 0, 7, 9 and 10 as well as on post-TAI Days 11 and 22. Results: The largest follicle diameter (LFD) was significantly larger (p < 0.05) in eventually diagnosed pregnant (EDP) than in eventually diagnosed non-pregnant (EDnP) buffaloes in all treatment protocols on Day 9. The serum progesterone (P4) concentration was significantly higher (p < 0.05) in either EDP or EDnP buffaloes in Noegestomet eCG6-ovysync compared with other protocols on Day 7. There was a highly significant (r=0.74, P<0.01) positive correlations between corpus luteum volume (CLV) and LFD in EDP buffaloes. Conclusions: It is concluded that modifying Basic-ovsync via P4 supplementation by injection of long-lasting P4 on Day 0 and insertion of Norgestomet ear implant from day 0 to day 7 plus an injection of eCG on Day 6 improve the fertility response in true anestrus in buffaloes.

Endocrine regulation of long-term enhancement of spermiation in meagre (Argyrosomus regius) with GnRHa controlled-delivery systems

Meagre (Argyrosomus regius) undergo spermatogenesis and spermiation when reared in captivity, but often produce low milt volumes, sometimes with reduced quality and for a limited time period. In the present study we a) compared the efficiency of gonadotropin releasing hormone agonist (GnRHa) implants versus injections on testicular stimulation and spermiation enhancement, b) investigated the effect of GnRHa on the endocrine spermiation regulation (sex steroid hormones), and c) evaluated a commercial induced spawning simulation scenario. Firstly, males (n = 5) were injected with 15.0 ± 0.2 μg GnRHa kg−1 (Injections) or implanted with 51.0 ± 5.1 μg GnRHa kg−1 (Implant) and compared their sperm production response. Secondly, the best hormonal treatment (Implant) was tested treating males (n = 8) with 57.5 ± 7.5 μg GnRHa kg−1 every 3 weeks for a period of 70 days. Milt production was improved by the GnRHa implants with only minor sperm quality alterations (improved sperm motility percentage). Elevated plasma testosterone (T) and 11-ketotestosterone (11-KT) levels were recorded in response to GnRHa implants, while no significant difference for 17,20β-dihydroxy-4-pregnen-3-one (17,20β-P) was observed. In the commercial induced spawning simulation, it was shown that meagre females are capable of on-demand induction of spawning at random intervals (5–21 days) using GnRHa injections, over a period of at least 2.5 months. During this period, spermiation enhancement was achieved with GnRHa implants every 3 weeks, producing sperm with stable, in general, quality and motility parameters. Percentage of motile cells, motility duration and density fluctuated significantly, but remained within levels that are considered appropriate for high fertilization success in this species.

Priming Before In Vitro Maturation Cycles in Cancer Patients Undergoing Urgent Fertility Preservation: a Randomized Controlled Study

In vitro maturation (IVM) of oocytes retrieved at germinal vesicle stage, followed by vitrification of mature oocytes, has emerged as a fertility preservation (FP) option. This technique was first developed for patients with polycystic ovarian syndrome. In this population, providing LH activity prior to oocyte collection has been associated with better IVM outcomes. However, the benefit of this treatment in normo-ovulatory breast cancer (BC) patients undergoing IVM for FP purpose has never been investigated. To assess if the absence of therapeutic intervention prior to oocyte retrieval for IVM modifies IVM outcomes in BC patients undergoing urgent FP, we performed a non-inferiority, randomized controlled trial. The main outcome was the total number of mature oocytes obtained and cryopreserved after IVM. A total of 172 normo-ovulatory women, suffering from BC, 18 to 39years of age received no injection or a subcutaneous injection of hCG or GnRH agonist (GnRHa) 36h before oocytes retrieval according to randomized allocation. The total number of cryopreserved oocytes were 5.1 ± 3.8, 5.4 ± 3.8, and 6.0 ± 4.2 oocytes, respectively in the without, hCG and GnRHa groups. Mean differences were not significant between the three groups (- 0.5; CI 97.5% [- 2.03:1.02] and - 0.22; CI 97.5% [- 1.75:1.32], respectively). Intention to treat analyses failed to show non-inferiority in the "without injection group" in comparison with hCG or GnRHa groups. Our results are not conclusive enough to modify our practices and to stop administering hCG or GnRHa before IVM cycles for FP. The study was retrospectively registered to clinical trial (ID NCT03954197) in May 2019.

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

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

Gamete quality and management for in vitro fertilisation in meagre (Argyrosomus regius)

The aquaculture of meagre (Argyrosomus regius) requires methods for the control of reproduction that enable the production of families from specific individuals for selective breeding programs. We experimentally determined the parameters required for an in vitro fertilisation protocol. A total of 14 females and 5 males (mean ± S.D. weights of 20.45 ± 6.22 and 15.94 ± 2.75 kg, respectively) were used. Selected females had vitellogenic oocytes >550 μm in diameter and males had fluid sperm upon application of abdominal pressure. Both sexes were treated with an injection of 15 μg kg−1 of gonadotropin-releasing hormone agonist (GnRHa) to induce oocyte maturation/ovulation and enhance sperm production. To determine the timing of ovulation and window of high egg viability, females were stripped serially every 2.5 h beginning 35 h after GnRHa treatment. Sperm was obtained 24 h after GnRHa treatment and was diluted 1/4 in modified Leibovitz for storage at 4 °C until use. Sperm quality parameters such as percentage initial spermatozoa motility, duration of motility, velocity and density were determined using computer assisted sperm analysis (CASA). In vitro inseminations were made in duplicate or triplicate batches of eggs from each spawn by mixing 0.5–1 mL of eggs, 20–40 μL diluted sperm (pooled from two males) and 100 mL of seawater. Fertilisation success was examined at spermatozoa (spz): egg ratios between ~2000 and 400,000 spz egg−1. The optimal time for stripping ovulated females was ≤3 h after ovulation, which was the window of optimal egg viability. Ovulation under the conditions of this study was close to 38 h after GnRHa treatment, with a range from 35 to 41 h. Beginning from 3 h after ovulation, egg viability declined probably due to overripening. Sperm diluted in Leibovitz maintained motility and velocity for as long as 7 h after collection. Spermatozoa motility (%) and average path velocity (VAP, μm/s) of sperm samples obtained from males before GnRHa injection declined rapidly after activation compared to the samples obtained 24 h post-injection, with significant decreases respectively after 75 and 45 s. A minimum ratio of 150,000 spermatozoa egg−1 was necessary to ensure high fertilisation success. The acquired knowledge of the present study will aid the aquaculture industry and future research on selective breeding programs for meagre.

Laparoscopic Surgery Combined with GnRH Agonist in Endometriosis.

To determine the efficacy of laparoscopic surgery combined with GnRH agonist (GnRH-a) in treating infertile patients with endometriosis (EMs), and analyze its effect on the levels of serum hormones and inflammatory factors of the patients. An experimental study. The Department of Urology, Zhongda Hospital, Southeast University, Jiang Su, China, from January 2015 to March 2016. One hundred and thirty infertile patients with EMs were randomly divided into a control group and an observation group with 65 cases in each group. Patients in the control group were treated by laparoscopic surgery, while patients in the observation group were added by the subcutaneous injection of GnRH-a, based on the treatment of the control group. Therapeutic effects, recurrence rates, and pregnancy rates between two groups were compared. Moreover, the levels of serum hormones estradiol (E₂), luteinizing hormone (LH), follicle stimulating hormone (FSH), inflammatory factors interleukin 17 (IL-17), interleukin 6 (IL-6), and tumor necrosis factor- (TNF-α) between two groups after treatment were compared. The total effective rate and pregnancy rate in the observation group were higher than those of the control group (p=0.009 and 0.002, respectively), and the recurrence rate was lower than that of the control group (p=0.008). After treatment, levels of serum E₂, LH, FSH in the observation group were lower than those of the control group (all p<0.001). Levels of serum IL-17, IL-6 and TNF-α were lower than those of the control group (all p<0.001). There was no statistically significant difference in adverse reactions between the two groups (p=0.730). Laparoscopic surgery combined with GnRH-a is a more effective treatment modality in endometriosis. It can reduce the serum levels of inflammatory factors in patients, improve their hormone level and pregnancy rate, and reduce the recurrence rate.

Clinical efficacy of GnRH-a combined with LNG-IUS in the treatment of refractory adenomyosis by magnetic resonance-guided high intensity focused ultrasound

Objective To explore the clinical effects of Gonadotropin releasing hormone agonist (GnRH-a) combined with levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of refractory adenomyosis by magnetic resonance-guided high intensity focused ultrasound (MRgHIFU). Methods 80 patients with refractory adenomyosis admitted to our hospital from April 2015 to June 2017 were randomly divided into observation group and control group. They were treated with MRgHIFU as observation group. LNS-IUS was placed after the third injection of GnRH-a as control group. The uterine volume, pain score, menstrual volume and adverse reactions were compared between the two groups at 3 and 6 months after treatment. Results After 6 months of treatment, the uterine volume of the observation group [(100.23±4.65)cm3] was significantly lower than that of the control group [(145.46±10.23)cm3], with statistically significant difference (t=6.01, P<0.05). After 6 months, the degree of dysmenorrhea in the observation group was significantly lower than that in the control group [(2.12±0.24)point vs (0.27±0.09)point], with statistically significant difference (t=5.21, P<0.05). At 3 and 6 months after treatment, the menstrual volume of the observation group was significantly lower than that of the control group [(64.67±10.12)point vs (96.45±15.12)point, (42.46±11.18)point vs (66.26±12.48)point], with statistically significant difference (t=4.51, P<0.05; t=3.58, P<0.05). The adverse reactions such as vaginal bleeding, hot flashes and night sweats were significantly lower than those in the control group (χ2=3.967, P<0.05). Conclusions As a new non-invasive and refractory treatment of adenomyosis, high intensity focused ultrasound guided by magnetic resonance is safe and effective with less adverse reactions, which is worthy of clinical application. Key words: Adenomyosis; Magnetic resonance imaging; Ultrasonography; Gonadotropin-releasing hormone; Levonorgestrel

Thermal manipulation and GnRHa therapy applied to the reproduction of lambari-do-rabo-amarelo, Astyanax altiparanae females (Characiformes: Characidae) during the non-breeding season

Lambari-do-rabo-amarelo Astyanax altiparanae in the wild reproduce during spring and summer, but females undergo vitellogenesis throughout the year, including the non-spawning winter period when water temperatures are low. The present study investigated the physiological role of temperature modulation on the hypothalamus-pituitary-gonads axis of lambari during winter, as well as the effects of gonadotropin releasing hormone agonist (GnRHa) therapy. Captive females were exposed to two different temperatures (20 °C and 27 °C) and were injected weekly with GnRHa for 21 days during winter (Control, CTR; Low dose; LD and high dose of GnRHa, HD). At the end of the 21-days period gonadosomatic index (GSI), oocyte stage of development and theoretical fecundity were evaluated, together with plasma levels of 17β-estradiol (E2). Gene expression of the two pituitary gonadotropins follicle-stimulating hormone (fshβ) and luteinizing hormone (lhβ), as well as hepatic vitellogenin-A (vtgA) expression were also analyzed. At the end of the experimental period, females from the six different experimental conditions were induced to spawn using human chorionic gonadotropin (hCG). Spawning performance parameters and plasma levels of the maturation inducing steroid (MIS) were analyzed. Gene expression of fshβ did not change with temperature manipulation, but females exposed to 27 °C and supplemented with a HD of GnRHa exhibited an increased fshβ gene expression, associated with higher E2 levels. The higher water temperature alone was able to increase E2 levels. At both water temperatures GnRHa injections induced a decrease in E2 levels. GnRHa injected females had a lower vtgA gene expression levels at 20 °C. Even with differences in the gene expression of gonadotropins among the various temperature/GnRHa treatments, GSI and oocyte diameter did not change, but GnRHa enhanced the number of vitellogenic oocytes at 20 °C. The reproductive performance of lambari induced to spawn with hCG was better after the combined treatment with GnRHa and summer temperature.

Effects of controlled ovarian stimulation on thyroid stimulating hormone in infertile women

ObjectiveTo study the effects of long-acting gonadotropin-releasing hormone agonist (GnRH-a) on thyroid function in euthyroid patients of in vitro fertilization (IVF)/ intracytoplasmic sperm injection of embryo transfer (ICSI-ET) and to investigate the timing and alteration of thyroid stimulating hormone (TSH) during controlled ovarian stimulation(COS). Materials and methodsEuthyroid patients scheduled for IVF/ICSI were enrolled. Euthyroidism was defined as having no history of hypothyroidism with normal TSH before IVF. Long GnRH-a protocol was chosen as COS protocol. 207 patients were divided into two groups based on basal serum TSH level: group A with 0.35mIU/L＜TSH＜2.5mIU/L (n = 137) and group B with 2.5mIU/L ≤ TSH＜4.5mIU/L (n = 70). Serum TSH was tested on 6 time points: before COS (2–5days in menstrual cycle, before GnRH-a injection), Gn injection day 1, Gn injection day 5, human chorionic gonadotropin (HCG) day, 14 and 28 days after transplantation. The serum TSH, clinical pregnancy and abortion rate were investigated. ResultThe serum TSH value was significantly (P < 0.05) increased after injection of long-acting GnRH-a in all patients. Both groups had significant (P < 0.05) increases in serum TSH level after long-acting GnRH-a injection. The TSH level was increased in 131(63.3%) patients after GnRH-a injection, of which twenty (9.7%) had subclinical hypothyroidism with TSH level over 4.5 mIU/L. The other 76 (36.7%) patients had decreased TSH. In group A, 79 (57.7%) patients showed an increase of TSH, including three patients (2.2%) with simultaneous rise of TPOAb and four (2.9%) diagnosed of subclinical hypothyroidism with TSH level over 4.5 mIU/L, and the rest fifty-eight (42.3%) patients had decreased TSH with one patient with elevated TPOAb who was diagnosed with subclinical hyperthyroidism. In group B, fifty-two (74.3%) patients showed an increase of TSH, including thirteen (18.6%) patients with elevated TPOAb and sixteen (22.9%) patients diagnosed of subclinical hypothyroidism with TSH level over 4.5 mIU/L, and the rest eighteen (25.7%) patients had decreased TSH with one patient diagnosed with subclinical hyperthyroidism. Group B had a significant higher proportion of patients with elevated serum TSH than group A (P ＜ 0.05). Compared to the baseline level, serum TSH ascended distinctly and reached peak level on HCG day in all patients. Group A and B had similar trends of alteration. Patients in group A had significantly (P＜0.05) higher clinical pregnancy rate than in group B. No significant (P＞0.05) difference in abortion rate were observed between the two groups. ConclusionGnRH-a can significantly increase serum TSH levels with possible development of subclinical thyroid dysfunction. Infertile patients with serum TSH > 2.5 mIU/L are more susceptible to GnRH-a while patients with basal TSH less than 2.5 mIU/L may get a higher clinical pregnancy rate when receiving IVF/ICSI.

Combined therapeutic effects of HIFU, GnRH-a and LNG-IUS for the treatment of severe adenomyosis

Objective: To evaluate the combined efficacy of high-intensity focused ultrasound (HIFU), gonadotropin-releasing hormone agonist (GnRH-a) and the levonorgestrel-releasing intrauterine system (LNG-IUS) for the treatment of severe adenomyosis.Method: Four hundred and sixty-six patients with adenomyosis admitted to the Department of Gynecology of Shanghai First Maternity and Infant Hospital underwent HIFU treatment, and then were consecutively administered with GnRH-a 1 d, 1 month and 3 months after HIFU treatment. The uterine size was then measured with ultrasound or MRI 2–4 weeks after three cycles of GnRH-a injection. The LNG-IUS was then inserted when the uterine length less than 9 cm. The visual analog scale (VAS), verbal rating scale (VRS), menstrual volume score, uterus volume, MRI, serum levels of hemoglobin and CA125 were measured at pre and 3-, 6-, 12-month post-HIFU.Results: Dysmenorrhea and menorrhagia significantly relieved after combined treatment with HIFU, GnRH-a and the LNS-IUS. The uterine volume shrank and returned to its normal size. The serum CA-125 level was reduced to the normal level after the combined treatment.Conclusions: The combined therapeutic regimen of HIFU, GnRH-a and LNS-IUS is safe, effective and efficient for curing severe adenomyosis.

Spawning kinetics and egg/larval quality of greater amberjack (Seriola dumerili) in response to multiple GnRHa injections or implants

The greater amberjack (Seriola dumerili) is one of the most promising finfish species for aquaculture, due to its cosmopolitan distribution and acceptability, high growth rates and large size. However, lack of reproduction control has been one of the main bottlenecks for its commercialization. The study examined two endocrine methods for the induction of oocyte maturation/ovulation and spawning, which are based on the induction of endogenous Luteinizing Hormone (LH) release from the pituitary, through the use of Gonadotropin Releasing Hormone agonist (GnRHa) either in the form of sustained-release delivery systems (implants) or injections (acute release). The stock (n = 28) consisted of wild fish captured in 2011 and each GnRHa administration method was conducted in two replicates, with 6 and 8 fish per tank, respectively, at a 1:1 sex ratio. Fish were given a GnRHa injection once a week (three administrations), or a GnRHa implant every 2 weeks (two administrations). Mean daily relative fecundity was significantly higher (t1.3 = −5.24, P = 0.012) in the implanted fish (15,170 ± 2,738 eggs kg−1 female day−1) compared to the injected fish (6,119 ± 2,790 eggs kg−1 female day−1). Total relative fecundity was also significantly higher (t1.3 = −9.93, P = 0.003) in the implanted fish (102,402 ± 20,337 eggs kg−1 female) compared to the injected ones (26,517 ± 9,938 eggs kg−1 female), but there were no differences in the quality of eggs in terms of fertilization, 24-h embryo survival, hatching and 5-d larval survival. The number of females with fully vitellogenic oocytes eligible for induction of spawning decreased from the initial to the final sampling, from 7 to 6 females for the GnRHa implant treatment and from 7 to 3 females for the GnRHa injection treatment. In addition to apparently promoting the proper endocrine changes leading to multiple cycles of oocyte maturation, ovulation and spawning, and thus producing larger numbers of eggs; the use of GnRHa implants may be more appropriate in greater amberjack than multiple injections because (a) it also stimulates vitellogenesis and (b) involves less handling of the fish.

103 Hormonal stimulation and post-breeding sperm induction in the mountain yellow-legged frog, Rana muscosa

The first choice of any captive animal program should be to promote natural breeding through appropriate diet and environmental conditions. However, in cases of poor reproductive performance, the administration of exogenous hormones can induce breeding behaviours and gamete release. Part of the approach to the Mountain yellow-legged frog recovery program is the collection of sperm for cryobanking as a means of preserving genetic diversity in a cost- and space-effective manner. To develop a protocol for induction of sperm release from Mountain yellow-legged frogs, we tested the administration of gonadotropin-releasing hormone agonist (d-Ala6, des-Gly10 ethylamide LHRH derivative) and hCG singly or in combination. Once a month, animals were injected with a single dose of saline amphibian ringers (control) or 1 of 10 hormone treatments. Groups 1-4 received a single intraperitoneal injection of gonadotropin-releasing hormone agonist administered in 4 different doses: (1) 0.3 μg/g body weight (bw); (2) 0.4 μg/g bw; (3) 0.6 μg/g bw; and (4) 1 μg/g bw. Groups 5 and 6 were injected with 5 and 10IU hCG/g bw, respectively, and groups 7-10 received a combined injection of hCG and GnRH in four different doses: (7) 5 IU/g hCG with 0.3 μg/g GnRH; (8) 10 IU/g hCG with 0.3 μg/g GnRH; (9) 5 IU/g hCG and 0.6 μg/g GnRH; and (10) 10 IU/g hCG and 0.6 μg/g GnRH. Hormone treatments began in July 2015, 2 months after the end of the breeding season to allow males a post-breeding recovery time. Monthly administration continued from July until December 2015, ending before the brumation period. In 2016, treatments resumed again in July, after another breeding period. In 2017, hormone treatments began in April, during the reproductive season, and continued until July. From July 2015 through November 2016, sperm concentration and motility were examined in response to hormones treatment groups 1, 3, 5, 6, and 7-10. In April 2017, based on previous results, experiments were redesigned to include group 9 from 2015-16, and two new groups, 2 and 4. Spermiation was not easily hormonally induced when administered from August-October 2015, August-September 2016, and in July 2017. These low-response periods coincided with post-breeding months when only 3.7% (3/81) of males responded to either 10 IU/g hCG, 0.6 μg/g GnRH, or a combination of 5 IU/g hCG and 0.6 μg/g GnRH. Sperm production was significantly affected (P&amp;lt;0.05) by the month of hormone administration and hormone treatments during the responsive periods (P&amp;lt;0.0001) of April-June and October-November. However, hormone doses and treatments had no significant effect on the average or total sperm concentration per male (P&amp;lt;0.05). Motility and speed of forward progression were not significantly affected by treatment (P&amp;lt;0.05). This study demonstrates the seasonality of sperm production in this species, which may be attributed to testicular recrudescence during the summer months following breeding. Without hormonal stimulation, spermiation did not occur during the nonreproductive part of the year.

Resolution of Uterine Arteriovenous Malformation and Maintenance of Reproduction in 20 Women Treated with a GnRH Agonist Concomitantly with an Aromatase Inhibitor and Tranexamic Acid.

This study investigated the efficacy of GnRH agonists concomitantly with transient aromatase inhibitor and tranexamic acid to treat women with uterine arteriovenous malformations (AVMs) associated with abnormal uterine bleeding (AUB) to preserve fertility and determine reproductive outcome. This was a prospective cohort study in a tertiary centre. Doppler ultrasound demonstrated AVM in 19 women with AUB 1-28 weeks following spontaneous or therapeutic abortion and in one woman 4 years after normal pregnancy while taking an oral contraceptive. On the basis of experience from the first three cases, 17 women were treated with tranexamic acid (1 g three times daily orally for 5 days), a GnRH agonist (3.75-11.25 mg, for 1-3 months), plus an aromatase inhibitor (letrozole 2.5 mg once daily for 5days) with the initial injection of GnRH agonist. Two women required blood transfusion, and one required uterine tamponade with Foley catheter balloon in the first 48 hours to control heavy bleeding (Canadian Task Force Classification II-2). All 20 AVMs resolved within 1-3 months of treatment. Of 16 women who attempted pregnancy, all (100%), including two who had uterine artery embolization (one after hysteroscopic septoplasty), conceived spontaneously with 18 live births. Two women are using contraception (one taking an oral contraceptive, one using a levonorgestrel intrauterine system), and one 40-year-old is not using contraception. One woman had hysteroscopic endometrial ablation followed by vaginal hysterectomy for AUB at 1 and 2 years later. A GnRH agonist in combination with transient aromatase inhibitor and tranexamic acid is an effective management strategy to treat and maintain reproduction in women with AVMs associated with AUB.

Influence of Estradiol Status on Physical Activity in Premenopausal Women.

This study aimed to determine the effects of 5 months of ovarian hormone suppression in premenopausal women on objectively measured physical activity (PA). Participants (age, 35 ± 8 yr; body mass index, 27 ± 6 kg·m) received monthly intramuscular injections of gonadotropin-releasing hormone agonist (GnRHAG) therapy, which suppresses pituitary gonadotropins and results in suppression of ovarian sex hormones. Women were randomized to receive concurrent transdermal E2 (GnRHAG + E2; n = 30) or placebo (GnRHAG + PL, n = 31). PA was assessed for 1 wk before and during each month of the 5-month intervention using a hip-worn accelerometer (Actical, Mini Mitter Co., Inc., Bend, OR). Estimates of time spent in sedentary, light, and moderate-to-vigorous PA (MVPA) were derived using a previously published equation. Subsets of participants in each group were also randomized to a supervised progressive resistance exercise training program. Total MVPA tended toward being higher (P = 0.08) in the GnRHAG + E2 group at month 4. There were no significant effects of intervention or time in sedentary or light PA. In the subset of women who did not participate in structured exercise training for which Actical data were obtained (n = 16 in each group), total MVPA was higher at month 4 (P = 0.01). PA levels seem to be maintained at a higher level in women undergoing pharmacological suppression of ovarian function with E2 add-back when compared with women treated with placebo. These data provide proof-of-concept data that E2 contributes to the regulation of PA in humans. However, given the exploratory nature of this study, future confirmatory investigations will be necessary.

Paired spawning with male rotation of meagre Argyrosomus regius using GnRHa injections, as a method for producing multiple families for breeding selection programs

Weekly gonadotropin-releasing hormone agonist (GnRHa) injections were used to induce spawning in paired male and female meagre (Argyrosomus regius) with a weekly rotation of the males, in order to produce a large number of families, as a method to facilitate selective breeding programs. Two different broodstocks were used (HCMR and IRTA), with females of mean weights of 11.7 ± 2.6 kg and 20.0 ± 1.8 kg, and males of 10.2 ± 1.2 kg and 15.1 ± 1.0 kg, respectively. A single GnRHa injection of 15 μg kg−1 was administered to each selected female, and 7.5 or 15 μg kg−1 to each male to induce spawning. In the subsequent weeks, maturity was checked and fish were induced as above, but males (n = 18) were rotated to form a different pair with the selected females (n = 21). Experiments finished when all paired combinations had been completed or a fish lost maturity status and could not be induced further. A total of 56 families were produced with a mean number of eggs from each family of 87,666 ± 11,244 eggs kg−1. There was a decline in the fecundity, number of spawns and percentage of pairs that spawned successfully after consecutive weekly GnRHa injections. Relative fecundity declined significantly from 134,495 ± 25,557 eggs kg−1 female body weight after the first injection, to 44,252 ± 17,638 eggs kg−1 after the fourth injection. However, there were no differences amongst weeks in egg fertilization success, hatching success or larval survival to 5 days post hatch. The decrease in fecundity and spawning success was attributed to a loss of maturity observed in the females, which may be related to differences in mate selection strategies between male and female meagre. The study demonstrated that paired spawning with male rotation was a successful method that can be used for breeding programs to produce a limit of three families per female or as a scaling up step to produce large numbers of offspring from a limited number of selected pairs.

Influence of extracellular environment on the motility and structural properties of spermatozoa collected from hormonally stimulated Panamanian Golden Frog (Atelopus zeteki)

A better understanding of the factors influencing the biology of amphibian spermatozoa after release from the testis is a prerequisite to the development of sperm preservation methods. The objective of the study was to determine the effect of extracellular conditions (exposure to water and different temperatures) over time on the sperm motility and structural properties (including morphology and DNA integrity) collected from hormonally stimulated Atelopus zeteki. Following intraperitoneal injection of gonadotropin-releasing hormone agonist (des-Gly10, D-Ala6, Pro-NHEt9 GnRH; 4 μg/g of body weight), human chorionic gonadotropin (hCG, 10 IU/gbw), or Amphiplex™ (0.4 μg/gbw GnRH-A + 10 μg/gbw metoclopramide hydrochloride), spermic urine samples from 27 males were collected and analyzed for sperm motility, morphology and DNA integrity while maintained at room temperature (23 °C), 4 °C, or diluted in water (hypo-osmotic environment) over a period of 46 min post-collection. Percentages of sperm motility and forward progressive motility remained high (>60%) when spermic urine was kept at room temperature or at 4 °C for 46 min regardless of the hormonal stimulation method. Dilution in water at room temperature greatly reduced the percentage of motile spermatozoa and forward progression (<50%) as well as DNA integrity (32.8% of intact cells) after 23 min while morphology did not differ (30.4% of normal cells), regardless of the hormone stimulation. This is the first systematic study on the effect of extracellular environment over time on A. zeteki sperm quality. This will contribute to the development of sperm handling protocols and reproductive technologies for this and other endangered Atelopus species.

Gonadotropin-Releasing Hormone Agonist Combined With a Levonorgestrel-Releasing Intrauterine System or Letrozole for Fertility-Preserving Treatment of Endometrial Carcinoma and Complex Atypical Hyperplasia in Young Women.

The aim of this study was to evaluate the efficacy and safety with gonadotropin-releasing hormone agonist (GnRHa) combined with a levonorgestrel-releasing intrauterine system or an aromatase inhibitor (letrozole) in young women with well-differentiated early endometrial carcinoma (EC) and complex atypical hyperplasia (CAH). We performed a retrospective analysis including the clinical characteristics of 29 patients younger than 45 years with early well-differentiated endometrioid adenocarcinoma of the uterus (EC) or CAH who were treated at the Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, from January 2012 to April 2016. Eighteen patients were treated with the combination of intramuscular injections of GnRHa every 4 weeks with the levonorgestrel intrauterine hormonal system (Mirena® Bayer Health Care Pharmaceutical Inc, Wayne, NY) was inserted. Eleven patients were treated with the combination of intramuscular injections of GnRHa every 4 weeks with oral letrozole 2.5 mg daily. The patients underwent follow-up with endometrial sampling by hysteroscopy and curettage for endometrial response every 3 months. After a median follow-up of 18.7 months (range, 5.6-54.9 months), 15 women (88.2%) in the EC group and 12 women (100%) in the CAH group had complete response (CR) after GnRHa combination treatment. Among the women who achieved CR, 1 woman (8.3%) with CAH and 1 woman (5.9%) with EC had recurrence after CR, and they finally underwent a hysterectomy. Time to CR was similar in the 2 groups (4.5 ± 1.9 months in the CAH group vs 5.0 ± 2.9 months in the EC group). Ten women (34.5%) had CR after the first 3 months, 8 women (27.6%) had CR after 6 months, and 9 women (31.0%) had CR after 9 months. Both GnRHa with the levonorgestrel-releasing intrauterine system and GnRHa with letrozole are alternative treatments for women with CAH and EC who desire fertility preservation. A larger multicenter trial of the fertility-preserving treatment is warranted.

Outcome of intracytoplasmic sperm injection after preinstillation of a gonadotropin releasing hormone agonist in the uterine cavity just before embryo transfer.

Objective:To evaluate the effects of a gonadotropin releasing hormone agonist (GnRHa) injection prior to embryo transfer on implantation and pregnancy rate.Materials and Methods:We performed a retrospective analysis of patients undergoing in vitro fertilization (IVF) therapy with and without GnRHa preinstallation into the uterine cavity just before embryo transfer between January 2012 and March 2013 in a single IVF center of a university hospital. Patients were evaluated based upon implantation, pregnancy, live birth, and miscarriage rates.Results:GnRHa was injected into the uterine cavity of 108 patients prior to embryo transfer which were regarded as study group. One thousand forty-seven patients who were not injected GnRHa were regarded as the control group. Pregnancy rates were 44.4% and 41.7% in the GnRHa and control groups, respectively. Live birth rates were 27.8% and 26.1%, miscarriage rates were 15.7% and 15.7%, and implantation rates were 31% and 30%, respectively and there were no difference between groups statistically (p>0.05).Conclusion:No statistically significant differences in implantation, pregnancy, live birth, or miscarriage rates were observed in patients treated with GnRHa prior to embryo transfer, relative to the controls. Therefore, GnRHa injection into the uterine cavity prior to embryo transfer is not recommended as a means of increasing implantation or pregnancy rates in IVF. However, prospective randomized controlled studies are needed to clarify the effect of GnRHa instillation in the uterine cavity for embryo implantation in IVF.

The effect of estradiol on granulosa cell responses to FSH in women with polycystic ovary syndrome

BackgroundThe influence of estradiol (E2) on granulosa cell (GC) function has not been tested clinically in women with polycystic ovary syndrome (PCOS). The objective of this study is to determine if E2 influences GC responses to FSH in women with PCOS.MethodsThis is a two phase, single cohort study conducted over a 2-year period at a single academic center. Nine women with PCOS according to NIH criteria. In Phase 1, FSH stimulation of GC responses as measured by E2 and Inhibin B (Inh B) were assessed before and at 5 and 6 weeks after GnRH agonist administration. In Phase 2, the same protocol was employed with the addition of an aromatase inhibitor (letrozole, LET) administered daily beginning at week 4 for 2 weeks.ResultsIn Phase 1, recovery of FSH, E2 and Inh B from ovarian suppression occurred at 5 and 6 weeks after GnRH agonist injection and preceded resumption of LH and androgen secretion. In Phase 2, hormone recovery after GnRH agonist was characterized by elevated FSH and suppressed E2 levels whereas recovery of LH and androgen levels were unchanged. In Phase 1, FSH stimulated E2 and Inh B responses were unaltered during recovery from ovarian suppression. In Phase 2, E2 and Inh B fold changes after FSH were significantly reduced at weeks 5 (p < 0.04) and 6 (p < 0.01), respectively.ConclusionIn anovulatory women with PCOS, chronic, unopposed E2 secretion may contribute, at least in part, to enhanced ovarian responsiveness to FSH.Trial registrationNCT02389088

Abdominal Scar Endometriosis and Hemothorax in a Nigerian Woman: A Case Report

We report here the unusual presentation of a 35-year-old nulliparous Nigerian teacher who presented with a 5- year history of primary infertility, painful menses and cyclical umbilical bleeding. Evaluation revealed a clinically stable woman with a midline, infra-umbilical surgical abdominal scar near the site of bleeding, a large right hemothorax on Chest X-ray, kissing ovaries on pelvic scan and abdominal mass on CT scan. Prior to presentation she had been histologically diagnosed with endometriosis in 2014 by laparoscopy and biopsy after several tests to rule out other conditions like tuberculosis. She had chest tube drainage of 800 ml of brownish, chocolatecolored fluid, 2 doses of GnRH agonist injection and eventually occlusion of the pleural space due to recurrence of hemothorax.