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Background The addition of a GnRH analogue to the luteal phase in in vitro fertilization programs has been seldom proposed due to the presence of GnRH receptors in the endometrium. The aim of the study was to evaluate the effect of triptorelin addition in short antagonist cycles, compared to cycles where the only supplementation was progesterone. Methods The primary objective of this study was the study of the effect of Triptorelin addiction during the luteal phase on the live birth rate. Secondary objectives of efficacy were pregnancy rates and implantation rates, as well as safety in terms of OHSS risks. The study was a prospective, randomized, open study, performed in two independent Centers from July 2013 to October 2015. Patients were divided into three groups: a) Regular antagonist protocol, with only luteal progesterone; b) Antagonist protocol with luteal triptorelin as multiple injections, c) Antagonist protocol with luteal triptorelin as single bolus. Descriptive statistics were obtained for all the parameters. Mean and standard deviation were used for all quantitative parameters. Differences between percentages were studied using Chi-square test generalized to the comparison of several proportions. Results A total number of 1344 patients completed the study, 786 under the age of 35 years, and 558 over 35 years. It was observed an increase of positive HCG results, Clinical pregnancy rates and Delivery rates when triptorelin was added in the luteal phase, irrespective whether as a single bolus or five injections. This increase was statistically significant both for pregnancy rates and delivery rates. The statistic difference between pregnancies and deliveries obtained with or without luteal triptorelin reached p  < 0,01. No increase of OHSS risk was observed. Conclusions From this large study it appears that the concept of luteal phase supplementation should be revisited. From our study it appears that triptorelin addition to the luteal phase of antagonist cycles, either as a single bolus or using multiple injections, is a good tool to optimize ART results. Trial registration The study was approved by the Ethics Committee of Provincia di Bergamo (n 1203/2013).

Purpose To compare the role of an aromatase inhibitor (letrozole) with a GnRH agonist (triptorelin) versus case control on the pregnancy rate and recurrence of symptoms and signs in patients with endometriosis. Methods In a prospective randomized clinical trial, after treatment of 144 infertile women in their reproductive age by laparoscopy (whose endometriosis was confirmed by prior laparoscopy), they were divided into 3 groups: group 1 (47 cases) who received letrozole for 2 months, group 2 (40 patients) who were prescribed triptorelin for 2 months and group 3 who were 57 patients in the control group and did not receive any medication. We followed up each group at least for 12 months after their restoration of regular cycle. Results Pregnancy rate was 23.4% in group 1, 27.5% in group 2, and 28.1% in group 3. The results did not show significant differences among the 3 groups . Recurrence rate of endometriosis was 6.4% in group 1, 5% group 2 and 5.3% in group 3, which was not statistically significantly different as well. Conclusion Pregnancy rate and endometriosis recurrence rate are comparable among the 3 groups.

Treatment with a luteinizing hormone–releasing hormone (LHRH) agonist increases adult height in children with precocious puberty. This study was designed to determine whether LHRH-agonist therapy would increase adult height in short adolescents with normally timed puberty. The adolescents had an increase of 0.6 in the standard-deviation score for height, as compared with the initially predicted adult height; however, bone mineral density was decreased. An LHRH agonist cannot be recommended. Puberty first accelerates the rate of growth and then induces epiphyseal fusion, terminating the growth of long bones. 1 In the 1970s, long-acting agonists of luteinizing hormone–releasing hormone (LHRH) were shown to suppress gonadotropin secretion. In children with LHRH-dependent precocious puberty, treatment with LHRH agonists slows bone maturation, delays epiphyseal fusion, and increases adult height. 2 – 7 Studies of patients with hypogonadotropic hypogonadism, 8 estrogen insensitivity, 9 or estrogen deficiency 10 have suggested that prolonging the period of growth by delaying senescence of the growth plate 11 can increase adult height. However, changes in the tempo of puberty within the normal range do not influence adult . . .

Introduction Luteinizing hormone-releasing hormone (LHRH) agonists (e.g., triptorelin) reduce ovarian estrogen production in premenopausal women with hormone-sensitive breast cancer. Aromatase inhibitors (e.g., exemestane) inhibit extraovarian production of estrogen and may further reduce circulating estrogens when combined with an LHRH agonist. Methods Healthy premenopausal women were randomized to receive 3.75 mg triptorelin (T) on days 1 and 29 with 25 mg exemestane (EX) or matched placebo once daily for 8 weeks, from day 1 to day 56. The primary objective was to evaluate the effect of T ± EX on estradiol (E₂) suppression by comparing the AUCday₃₆₋₅₇ for the 2 treatments. Secondary objectives included evaluation of estrone (E₁), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) suppression; effects of EX on the T-induced gonadotrophin and estrogen flare; pharmacokinetics (PK); and safety. Results Twenty-eight (14 in each arm) were evaluable for efficacy and PK. Mean plasma estrogen levels (AUCday₃₆₋₅₇) were significantly lower for subjects who received T + EX than for subjects who received T alone (20.6 vs. 54.0 pg d/ml [-62%; P < 0.05], and 38.9 vs. 198.0 pg d/ml [-80%; P < 0.01] for E₂ and E₁, respectively). Coadministration of EX did not affect the initial flare or subsequent suppression of LH and FSH following the first dose of T, or the PK of T. Both treatments were well tolerated. Conclusions Coadministration of T and EX resulted in greater estrogen suppression than when T was given alone. These findings could translate into improved clinical outcomes for premenopausal breast cancer patients receiving LHRH agonists.

Abstract Context Hormonal interventions in adolescents with gender dysphoria may have adverse effects, such as reduced bone mineral accrual. Objective To describe bone mass development in adolescents with gender dysphoria treated with gonadotropin-releasing hormone analogues (GnRHa), subsequently combined with gender-affirming hormones. Design Observational prospective study. Subjects 51 transgirls and 70 transboys receiving GnRHa and 36 transgirls and 42 transboys receiving GnRHa and gender-affirming hormones, subdivided into early- and late-pubertal groups. Main Outcome Measures Bone mineral apparent density (BMAD), age- and sex-specific BMAD z-scores, and serum bone markers. Results At the start of GnRHa treatment, mean areal bone mineral density (aBMD) and BMAD values were within the normal range in all groups. In transgirls, the mean z-scores were well below the population mean. During 2 years of GnRHa treatment, BMAD stabilized or showed a small decrease, whereas z-scores decreased in all groups. During 3 years of combined administration of GnRHa and gender-affirming hormones, a significant increase of BMAD was found. Z-scores normalized in transboys but remained below zero in transgirls. In transgirls and early pubertal transboys, all bone markers decreased during GnRHa treatment. Conclusions BMAD z-scores decreased during GnRHa treatment and increased during gender-affirming hormone treatment. Transboys had normal z-scores at baseline and at the end of the study. However, transgirls had relatively low z-scores, both at baseline and after 3 years of estrogen treatment. It is currently unclear whether this results in adverse outcomes, such as increased fracture risk, in transgirls as they grow older.

The treatment of paraphilias, especially of pedophilia, centers upon cognitive-behavioral psychotherapy and pharmacologic interventions. Two open, uncontrolled clinical studies using the synthetic LHRH-agonist triptorelin suggested that, combined with psychotherapy, antiandrogen treatment reduced deviant sexual fantasies, urges, and behaviors in paraphilic patients. There is a need for further research using controlled, randomized trials to examine the effectiveness of sexual offender treatment including psychotherapeutic and pharmacologic interventions. The aim of this pilot study is to evaluate the efficacy and tolerability of cognitive-behavioral psychotherapy together with intramuscular (IM) 3-monthly injections of triptorelin in adult men with severe pedophilia. In this multicenter, forensic psychiatric hospital-based, double-blind, controlled, parallel group phase IV trial conducted in Germany, convicted male sexual offenders aged ≥ 18 years with pedophilia, as defined by DSM-IV-TR criteria, will be randomized to receive study-specific psychotherapy together either with triptorelin or placebo for 12 months (total of 4 injections). This is a pilot study, therefore exploratory data analyses will be carried out of three different target parameters: 1. Changes in psychosexual characteristics using the Multiphasic Sex Inventory (scale: sexual abuse of children) 2. Changes in the risk of violent sexual behavior using the Sexual Violence Risk-20 total score 3. Changes in serum testosterone concentration Treatment effects will be assessed by comparing baseline values with those at the final examination (month 12). The absence of real-life stimulants to test for actual recidivism limits possible findings. The study will be conducted in agreement with the European GCP-guideline, all relevant legal requirements, and the legal framework for voluntary treatment of convicted sexual offenders in Germany.

We aim to provide a translational model to investigate the reproductive consequences of pubertal delay using the GnRH agonist triptorelin in transgender girls, tested in particular on testicular maturation in peripubertal rats. A total of 30 Sprague Dawley rats were utilized, with 10 subjects assigned to each of three groups from day P30 postpartum (prepubertal) until day P95 (postpubertal), mimicking treatment timing in patients. Rats received triptorelin at three time points (P30, P50, and P71), or only at P30 and P50. Control rats were injected with vehicle. Plasma testosterone levels were determined using MRM analysis. Testes and epididymides were examined histologically. There were significantly lower testosterone levels at postnatal day 48 in treated rats, indicating delayed puberty, with further reductions by day 69. By day 93, testosterone levels had recovered in rats given vehicle at P71 but remained low in the triptorelin-continuous group, suggesting the reversibility of the treatment. Treated rats had smaller testes; however, the majority of the testicular parenchyma was unaffected, with most seminiferous tubules displaying complete spermatogenesis. However, focal atrophic changes were observed in 1–30% of the parenchyma. One-third of the short-term group and half of the long-term group were classified as atrophic. Despite these changes, all treated rats had mature sperm in the epididymis, ensuring their fertility. In conclusion, triptorelin treatment promotes a decline in testosterone levels accompanied by discrete atrophy of the seminiferous tubules, which is partially reversible and compatible with sperm production and fertility preservation. Triptorelin could be an appropriate treatment prior to estrogen therapy for patients seeking gender transition.

Introduction Precocious puberty (PP) in girls is defined by thelarche before age 8. The diagnostic gold standard is an increased LH level following gonadotropin-releasing hormone (GnRH) stimulation. Alternatively, GnRH analogues like triptorelin can be used, though their interpretation varies. Since 2000, we have used a triptorelin-induced LH cut-off of 15 IU/L, 4 h post-stimulus. However, many girls showed LH values below this threshold despite evident pubertal progression. Purpose To establish a new LH threshold post-triptorelin stimulation for earlier diagnosis of central precocious puberty (CPP) in girls showing pubertal progression and to evaluate additional parameters for diagnostic accuracy. Methods We enrolled 186 girls with thelarche onset between ages 1–8 and a GnRH analogue assay performed between 2015–2019 without signs of axis activation. Within this cohort, 62 patients repeated the triptorelin test due to rapid pubertal progression. The assay involved administering 100 mcg/m² of triptorelin and measuring LH, FSH, and estradiol levels before and four hours post-injection. Results Patients with axis activation at the second test had significantly higher post-stimulus LH levels at the first test compared to those below 15 IU/L. They also had higher basal LH levels, elevated LH/FSH ratio, and increased growth velocity. Statistical analysis identified a new post-stimulus LH threshold of 5 IU/L. Conclusion We propose a LH value of 5 IU/L after triptorelin administration as a new threshold for early CPP diagnosis. While the LH/FSH ratio and growth velocity are associated with axis activation, they did not significantly enhance diagnostic accuracy when combined with the LH value.

The reproductive physiology of canines is unique from other mammals because oocyte maturation occurs about 48-72 hours after ovulation. This study aimed to evaluate the blood serum protein profile in canines during the periovulatory period by using shotgun proteomics to identify potential biomarkers of oocyte maturation. Anestrus female dogs (  = 9) were implanted subcutaneously with 4.7 mg of deslorelin to induce estrus and ovulation. After implantation, ovariectomy was performed based on the level of progesterone and vaginal cytology evaluations conducted every 48 hours. Simultaneously, serum samples were collected for proteomic analysis. The oocytes were flushed from the oviduct, and the oocyte maturation stage was identified. Based on oocyte staging, all samples were categorized into three groups (  = 3 dogs per group): pre-ovulation, ovulation with immature oocytes, and ovulation with mature oocytes. All serum samples were analyzed in triplicate (27 independent injections) using liquid chromatography-tandem mass spectrometry to investigate the protein profile. Proteomics analysis showed 11 proteins upregulated from three different groups: tubulin-specific chaperone D (TBCD); coiled-coil domain-containing protein 93 (CCDC93); WDFY family member 4 (WDFY4); calcium and integrin-binding protein 1 (CIB1); IQ motif containing E (IQCE); large ribosomal subunit protein uL23 N-terminal domain-containing protein (RPL23A); neuraminidase 4 (NEU4); G protein-coupled receptor kinase (GRK3); NF-keppaB inhibitor delta (NFKBID); leucine rich repeat containing 4B (LRRC4B); and Rho family-interacting cell polarization regulator 2 (RIPOR2). Among these proteins, NFKDIB, which are oocyte maturation markers in other mammalian species, was upregulated in the ovulation with mature oocyte group (  < 0.01). Therefore, NFKBID is a possible to be an oocyte maturation marker in canines, but further studies on larger populations are needed to confirm its potential.

Dydrogesterone (DYG) has been demonstrated to be an alternative progestin in the progestin-primed ovarian stimulation (PPOS) protocol with comparable oocyte retrieval and pregnancy outcomes. However, its safety regarding neonatal outcomes and congenital malformations is still unclear. This retrospective cohort study included 3556 live-born infants after in vitro fertilization and vitrified embryo transfer cycles using the DYG + human menopausal gonadotropin (hMG) protocol (n=1429) or gonadotropin-releasing hormone (GnRH)-agonist short protocol (n=2127) from January 2014 to December 2017. Newborn information was gathered from standardized follow-up questionnaires and/or access to medical records within 7 days after birth. Associations between ovarian stimulation protocols and outcome measures were analyzed by binary logistic regression after adjusting for confounding factors. In both singletons and twins, birth characteristics regarding mode of delivery, newborn gender, gestational age, birthweight, length at birth and Z-scores were comparable between the two protocols. For adverse neonatal outcomes, the two protocols showed no significant differences on the rates of low birthweight, very low birthweight, preterm birth, very preterm birth, small-for-gestational age, large-for-gestational age and early neonatal death after adjustment. Furthermore, the incidence of major congenital malformations in the DYG + hMG protocol (1.12%) was similar to that in the GnRH-agonist short protocol (1.08%), with the adjusted odds ratio of 0.98 (95% confidence interval [CI]: 0.40-2.39) and 0.90 (95% CI: 0.33-2.41) in singletons and twins, respectively. Our data suggested that compared with the conventional GnRH-agonist short protocol, application of DYG in the PPOS protocol was a safe option for the newborn population without compromising neonatal outcomes or increasing congenital malformation risks.