Efficacy of Triptorelin 3-Month Depot Compared to 1-Month Depot for the Treatment of Korean Girls with Central Precocious Puberty in Single Tertiary Center.

BACKGROUND: Triptorelin depot is largely used to treat central precocious puberty (CPP) in children, and a 3-month depot has been introduced. However, data about the 3-month gonadotropin-releasing hormone use for treatment of CPP in Korean girls are not available. This study was conducted to compare the efficacy of a triptorelin 11.25 mg 3-month depot with that of a 3.75 mg 1-month depot in suppressing pubertal development for the treatment of CPP. METHODS: A retrospective study, including 106 girls with CPP treated with triptorelin, was conducted. Fifty patients were treated with a triptorelin 3-month depot, and 56 were treated with a triptorelin 1-month depot. Serum luteinizing hormone (LH), follicle-stimulating hormone, and estradiol levels were analysed every 6 months after the visit. The height and bone age of each patient was evaluated at the beginning of treatment, after 6 months, and one year after therapy. RESULTS: The baseline characteristics of the girls treated with a 3-month depot were similar to those of the girls treated with a 1-month depot. A suppressed levels of LH to the triptorelin injection (serum LH < 2.5 IU/L) at 6 months was seen in 90.0% and 98.2% of the girls treated with the 3-month and 1-month depots, respectively (P = 0.160). After 1 year of treatment, a suppressed levels of LH was seen in 93.5% and 100% of the girls treated with the 3-month and 1-month depots, respectively (P = 0.226). Height velocity showed no significant difference between the two groups. Degree of bone age advancement decreased from 1.22 ± 0.07 and 1.22 ± 0.08 years at baseline (P = 0.914) to 1.16 ± 0.07 and 1.17 ± 0.08 in the girls treated with the 3-month and 1-month depots after 1 year, respectively (P = 0.481). CONCLUSION: This study showed that the efficacy of long-acting triptorelin 3-month was comparable to 1-month depot regarding hormonal suppression and inhibition of bone maturation. The triptorelin 11.25 mg 3-month depot is an effective treatment for girls with CPP.

Pregnancy outcome and cost-effectiveness comparisons of artificial cycle-prepared frozen embryo transfer with or without GnRH agonist pretreatment for polycystic ovary syndrome: a randomised controlled trial.

OBJECTIVE: To compare the live birth rate and cost effectiveness of artificial cycle-prepared frozen embryo transfer (AC-FET) with or without GnRH agonist (GnRH-a) pretreatment for women with polycystic ovary syndrome (PCOS). DESIGN: Open-label, randomised, controlled trial. SETTING: Reproductive centre of a university-affiliated hospital. SAMPLE: A total of 343 women with PCOS, aged 24-40 years, scheduled for AC-FET and receiving no more than two blastocysts. METHODS: The pretreatment group (n = 172) received GnRH-a pretreatment and the control group (n = 171) did not. Analysis followed the intention-to-treat (ITT) principle. MAIN OUTCOME MEASURES: The primary outcome measure was live birth rate. Secondary outcome measures included clinical pregnancy rate, implantation rate, early pregnancy loss rate and direct treatment costs per FET cycle. RESULTS: Among the 343 women randomised, 330 (96.2%) underwent embryo transfer and 328 (95.6%) completed the protocols. Live birth rate according to ITT did not differ between the pretreatment and control groups [85/172 (49.4%) versus 92/171 (53.8%), absolute rate difference -4.4%, 95% CI -10.8% to 2.0% (P = 0.45). Implantation rate, clinical pregnancy rate and early pregnancy loss rate also did not differ between groups, but median direct cost per FET cycle was significantly higher in the pretreatment group (7799.2 versus 4438.9 RMB, OR = 1.9, 95%CI 1.2-3.4, P < 0.001). Median direct cost per live birth was also significantly higher in the pretreatment group (15663.1 versus 8189.9 RMB, odds ratio [OR] = 1.9, 95% CI 1.2-3.8, P < 0.001). CONCLUSIONS: Pretreatment with GnRH-a does not improve pregnancy outcomes for women with PCOS receiving AC-FET, but significantly increases patient cost. TWEETABLE ABSTRACT: For women with PCOS, artificial cycle-prepared FET with GnRH agonist pretreatment provides no pregnancy outcome benefit but incurs higher cost.

Angiogenic cytokine and interleukin 8 levels in early luteal phase after triggering ovulation with gonadotropin-releasing hormone agonist in high-responder patients.

PROBLEM: Interleukin 8 (IL-8), vascular endothelial growth factor A (VEGFA), its receptors 1 (VEGFR1) and 2 (VEGFR2) are associated with ovarian hyperstimulation syndrome (OHSS) pathophysiological mechanisms. The aim of this study was to evaluate the concentrations of these cytokines depending on the way of ovulation triggering. METHOD OF STUDY: A total of 51 high-responder patients underwent IVF program and received gonadotropin-releasing hormone agonists (GnRHa) trigger + 1500 IU human chorionic gonadotropin (hCG) support on the oocyte pick-up (OPU) day (group I), dual trigger (GnRHa + 1500 IU hCG; group II), or hCG trigger 10,000 IU (group III) for the final oocyte maturation. The concentrations of cytokines were evaluated in serum by the enzyme-linked immunosorbent assay kit. RESULT(S): VEGFR2 levels were significantly lower in groups I and II than in group III in serum on the OPU (I vs. III, p = .0456; II vs. III, p = .0122) and OPU + 5 day (I vs. III, p = .0004; II vs. III, p = .0082). VEGFA levels were lower in group I than in group III (p = .0298) on the OPU day, however, were similar in all groups on the OPU + 5 day. CONCLUSION(S): A small dose of hCG elicits similar concentrations of VEGFA to a full dose of hCG; however, GnRHa triggering reduces the concentrations of VEGFR2, which could lead to the OHSS prevention.

The effect of adenomyosis on IVF after long or ultra-long GnRH agonist treatment.

RESEARCH QUESTION: Does adenomyosis affect IVF independent of decreased ovarian reserve, and what are the characteristics and IVF outcome of the ultra-long gonadotrophin-releasing hormone (GnRH) agonist protocol in adenomyosis? DESIGN: Observational cohort study of three groups of patients undergoing first cycle of IVF treatment with normal ovarian reserve: (A) 362 patients with adenomyosis using the ultra-long GnRH agonist protocol; (B) 127 patients with adenomyosis using the long GnRH agonist protocol; (C) 3471 patients with tubal infertility using the long GnRH agonist protocol. RESULTS: Compared with groups B and C, the number of oocytes retrieved in group A decreased, and the gonadotrophin dosage and duration in group A were higher (P < 0.001). In long GnRH agonist treatment, clinical pregnancy rate (OR 0.492, 95% CI 0.327 to 0.742, P < 0.001), implantation rate (OR 0.527, 95% CI 0.350 to 0.794, P = 0.002) and live birth rate (OR 0.442, 95% CI 0.291 to 0.673, P < 0.001) decreased and miscarriage rate (OR 3.078, 95% CI 1.593 to 5.948, P < 0.001) increased in adenomyosis patients compared with tubal infertility. For adenomyosis patients, clinical pregnancy rate (OR 1.925, 95% CI 1.137 to 3.250, P = 0.015), implantation rate (OR 1.694, 95% CI 1.006 to 2.854, P = 0.047) and live birth rate (OR 1.704, 95% CI 1.012 to 2.859, P = 0.044) increased in the ultra-long GnRH agonist treatment compared with long GnRH agonist treatments. CONCLUSION: Adenomyosis could negatively affect IVF outcomes independent of ovarian reserve after long GnRH agonist protocol. Patients with adenomyosis following the ultra-long GnRH agonist protocol could have a better pregnancy outcome than those following the long GnRH agonist protocol.

Relapse after conservative surgery combined with triptorelin acetate versus conservative surgery only in women with focal adenomyosis: study protocol for a multicenter, prospective, randomized controlled trial.

BACKGROUND: The preservation of fertility and integrity of the reproductive organs has increasingly been of concern to most women with adenomyosis. Adenomyomectomy is conservative surgery that is now widely applied; however, relapse is a serious problem after the operation. Postoperative treatment, such as gonadotropin-releasing hormone agonist (GnRHa) has been suggested to result in reducing the rate of disease recurrence. However, there is still a lack of evidence from randomized clinical trials examining the efficacy of GnRHa in decreasing the postoperative recurrence rate. METHOD/DESIGN: Relapse after conservative surgery combined with triptorelin acetate versus conservative surgery only in women with focal adenomyosis is a multicenter, prospective, randomized controlled trial. The primary outcome is relapse assessed using a visual analogue scale (VRS) and numeric rating scale (NRS), pictorial blood loss assessment chart (PBAC) score, and the size of the uterus and the lesion as measured by two/three-dimensional color doppler ultrasonography (2D/3D-CDUS) or magnetic resonance imaging (MRI). The secondary outcomes include quality of life, clinical pregnancy, ovarian reserve, adverse events, assessment by the Short Form (36) Health Survey and Female Sexual Function index, serum follicle-stimulating hormone, estradiol levels, and anti-Muellerian hormone and so on. All these indexes are measured at 3, 6, 12, 18, 24, 30, and 36 months after conservative surgery. DISCUSSION: The result of this large, multicenter randomized trial will provide evidence for one of the strategies of long-term management in focal adenomyosis after conservative operation. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1800014340. Registered on 6 January 2018.

Fertility outcome after medically treated pyometra in dogs.

Cystic endometrial hyperplasia-pyometra complex (CEH/P) is a challenge in canine reproduction. Present study aimed to assess fertility after medical treatment. One-hundred-seventy-four bitches affected by CEH/P received aglepristone on days 1, 2, 8, then every 7 days until blood progesterone < 1.2 ng/mL; cloprostenol was administered on days 3 to 5. Records were grouped according to bodyweight (BW): small (< 10 kg, n = 33), medium (10 ≥ BW < 25 kg, n = 44), large (25 ≥ BW < 40 kg, n = 52), and giant bitches (BW ≥ 40 kg, n = 45). Age; success rate; aglepristone treatments number; relapse, pregnancy rates; diagnosis-relapse, -first, -last litter intervals; litters number after treatment, and LS were analyzed by ANOVA. Overall age was 5.14 ± 1.75 years, without difference among groups. Treatment was 100% successful, without difference in treatments number (4.75 ± 1.18), relapse (15/174, 8.62%) and pregnancy (129/140 litters, 92.14%) rates, intervals diagnosis-relapse (409.63 ± 254.9 days) or -last litter (418.62 ± 129.03 days). The interval diagnosis-first litter was significantly shorter (163.52 ± 51.47 days) and longer (225.17 ± 90.97 days) in small and giant bitches, respectively. Overall, 1.47 ± 0.65 litters were born after treatment. Expected LS was achieved in each group, as shown by ΔLS (actual-expected LS by breed, overall -0.40 ± 1.62) without differences among groups. Concluding, CEH/P affects younger dogs than previously described. Relapses were rarer than previously reported. Medical treatment with aglepristone+cloprostenol is effective and safe, preserving subsequent fertility, as demonstrated by negligible changes in LS.

[Endocrine adjuvant treatment specific features for young breast cancer women]. / Particularités de l'hormonothérapie adjuvante de la femme jeune.

For young patients with hormone receptor-positive early breast cancer, tamoxifen for at least 5 years is the standard endocrine treatment. Prolonged endocrine treatment over 5 years is recommended for patients with high risk of late relapse. When adjuvant chemotherapy is indicated, prolonged iatrogenic amenorrhea is a strong pronostic factor. WIthout persistant amenorrhea after chemotherapy, it is indicated to associate ovarian suppression to the endocrine treatment. Optimal duration of this induced amenorrhea is unknown.

A multi-center, randomized controlled clinical trial of the application of a shortened protocol of long-acting Triptorelin down-regulated prior to IVF/ICSI among patients with endometriosis: A protocol.

BACKGROUND: Endometriosis is the major cause of progressive pelvic pain and subfertility. Up to 50% of reproductive-age women suffer from pelvic pain. Endometriosis is a classic indication for IVF. Compared with women whose inability to procreate is caused by simple tubal infertility, women with endometriosis often have lower pregnancy rates following in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). The administration of gonadotrophin-releasing hormone (GnRH) agonists prior to IVF/ICSI can improve the successful pregnancy rate. Whether a briefer treatment interval would be efficacious has not been studied. METHODS/DESIGN: Eligible and consenting women will be randomly assigned to one of two treatments (one cycle of a GnRH agonist or two cycles of a GnRH agonist) prior to IVF/ICSI using a table of random numbers. The primary outcome of this trial is clinical pregnancy rate. Other outcomes include gonadotrophin (Gn) duration, the total dose of follicle-stimulating hormone (FSH) used, number of oocytes retrieved, number of embryos available for transfer, implantation rate, the abortion rate, live birth rate, and incidence of moderate-to-severe ovarian hyperstimulation. The sample size of this trial is estimated to be 421 participants for each of the two arms. Appropriate interim analyses will be conducted by a data monitoring and ethics committee (DMEC), and the final test will be an intention-to-treat analysis. TRIAL REGISTRATION: This trial has been assigned the following registry number: NCT03006406 .

[Pneumothorax catamenial: results of 18 cases operas]. / Pneumothorax catamenial: resultats de 18 cas opérés.

This study aims to propose a therapeutic approach for catamenial pneumothorax based on outcomes reported in 18 cases. We conducted a retrospective study of 18 female elderly patients with an average age of 32.2 years who had undergone surgery for right (16 cases) and bilateral catamenial pneumothorax (2 cases) from January 1994 to December 2016. The patients were divided into 3 groups on the basis of the evolution of our surgical capability over time: group 1(G1) from January 1994 to June 2006, group 2 (G2) from July 2006 to February 2008, group 3(G3) from March 2008 to December 2016, these groups were composed of 5, 2 and 11 patients respectively. All these patients were nulliparous who had suffered from dysmenorrhoea associated, in 11 cases, to catamenial chest pain since puberty. Standard radiographic evaluation of the chest was sistematically performed and complemented, in 8 cases, by chest CT scan that showed apical bubbles in addition to pneumothorax (5 cases). Exploration through posterolateral mini-thoracotomy (16 cases) and through videothoracoscopy (2 case of G3) showed diaphragmatic fenestrations (18 cases) and bubbles (5 cases). Biopsy of lesions as well as resection of the bubbles were sistematically performed . Surgical treatment of diaphragmatic fenestrations was based, in group 1, on resection-suture with pleural abrasion, in group 2, on Gore-tex patches coverage with pleural abrasion and, in group 3, on patch coverage with pleural talcage. Each patient underwent hormone therapy (triptoreline) for 6 months during postoperative period, in order to suspend menstruations. Surgical outcomes were evaluated on the basis of the recurrence or non-recurrence of a pneumothorax after resumption of menstruations. Mortality was zero. Postoperative hospital length of stay was 9.32 days. Anatomo-pathological examinations confirmed thoracic endometriosis in 9 cases. After a mean follow-up period of 5.3 years, outcomes were good in 12 patients (3/5 in G1, 1/2 in G2 and 8/11 in G3); 3 patients in G3 continued to have minimal episodes of dyspnoea at the beginning of some menstrual cycles without radiological evidence of recidivism, 3 patients (2 in G1 and 1 in G2) had recurrences requiring reoperation. We recommend phrenoplasty using patches associated with pleural talcage and complementary concomitant hormone therapy for 6 months in patients suffering from catamenial pneumothorax with diaphragmatic fenestrations.

Deslorelin Implant Treatment for Hair Cycle Arrest (Alopecia X) in Two Intact Male Keeshonden.

Alopecia in dogs occurs secondary to a variety of underlying inflammatory and noninflammatory conditions. Hair cycle arrest (alopecia X) is a noninflammatory alopecia that is frustrating to diagnose and treat due to lack of understanding of disease pathogenesis. A variety of therapies for hair cycle arrest have been described with inconsistent efficacy in different dog breeds and sexes; no definitive treatment is available. This report describes the use of a deslorelin acetate implant in two sexually intact adult male keeshonden, both diagnosed with hair cycle arrest. The dogs had progressive alopecia of the trunk that spared the head and distal limbs present for at least 2 yr. Diagnosis of hair cycle arrest was made based on clinical features, dermatohistopathology, and lack of systemic abnormalities. Treatment with a single subcutaneous 4.7 mg deslorelin acetate implant resulted in profuse hair regrowth within 3.5 mo that endured for at least 14 mo. Deslorelin implantation is a management option that is safe, affordable, and appears effective for sexually intact male keeshonden with hair cycle arrest.

Assessment of stress levels in girls with central precocious puberty before and during long-acting gonadotropin-releasing hormone agonist treatment: a pilot study.

BACKGROUND: The objective of the study was to determine the stress levels of girls with central precocious puberty (CPP) before and during treatment with a long-acting gonadotropin-releasing hormone agonist (GnRHa). METHODS: The Child Stress Scale (CSS) was used for 10 unrelated girls with CPP before and after the first year of GnRHa treatment. The CSS is divided into four subscales (physical, psychological, psychological with depressive component and psychophysiological reactions). Through a quantitative analysis, it is possible to classify stress into four stages: alarm, resistance, near-exhaustion and exhaustion. RESULTS: At diagnosis, 90% of the girls showed stress levels scores at the alarm or resistance stage on at least one subscale, mostly in terms of physical and psychological reactions. The mean total stress score was significantly higher before when compared to after GnRHa treatment (43.4±15.6 vs. 28.9±9.7; p<0.05). The mean stress scores obtained in all subscales, except the one on psychophysiological reactions, were significantly higher before GnRHa treatment. CONCLUSIONS: Higher stress levels were a common finding in girls with CPP before treatment. The significant stress level reduction after pubertal suppression reinforces the idea that sexual precocity is a stressful condition in children. The CSS might be a useful tool for psychological assessment of patients with CPP.

Efficiency of GnRH analogues in treating large functional ovarian cysts.

AIM: The aim of this study was to determine the potential therapeutic benefit of a single administration of a GnRH analogue in pre- menopausal women presenting large functional ovarian cysts (FOCs) (diameter > five cm). MATERIALS AND METHODS: Fifty-one patients (median age 37.4 years) diagnosed with ovarian cysts, presumed benign based on transvaginal and/or transabdominal ultrasound, were divided in three study groups. Patients of group A received no medication whereas patients of groups B and C were treated with a single administration of a GnRH analogue and combined oral contraceptives, respectively. Patients were re-examined after a three-month period. Three of the 51 patients were lost in follow-up or stopped the treatment. RESULTS: Complete resolution of the ovarian cysts was observed in eight (50%), 14 (70%), and eight (67%) patients of groups A, B, and C, respectively. No side effects were observed in either of the three groups. The positive therapeutic effect in group B did not reach statistical significance compared with the two other groups (p > 0.05). CONCLUSION: Anew option of treating large FOCS through a single-dose of a GnRH analogue is proposed and should be carefully considered. Further research is needed in order to evaluate GnRH analogues as an alternative treatment.

Ovulation induction and luteal support with GnRH agonist in patients at high risk for hyperstimulation syndrome.

The aim of this study was to compare GnRHa trigger and luteal addition of triptorelin to hCG trigger for final oocyte maturation in women at high risk for OHSS undergoing IVF. A total of 423 patients were divided in two groups both stimulated using antagonist short protocol. Gonadotropins 75-150 UI/day were started on day 2-5, GnRH antagonist was added when the lead follicle was >14 mm and the final trigger was obtained with hCG 250 µg or triptorelin 0.2 mg. The luteal phase was supported with progesterone alone in the hCG group, with progesterone plus triptorelin 0.1 every other day from embryo transfer in the triptorelin group. In the triptorelin group we did neither have to suspend any embryo transfer, nor we have any early clinical OHSS. In the control group, 13 patients were suspended due to symptomatic high risk for OHSS and two patients developed a clinically significant OHSS. No statistically significant difference was observed in terms of clinical and ongoing pregnancy rates and implantation rates. Our results indicate that a protocol including GnRHa as trigger and an intensive luteal phase supported with GnRHa is safer than a standard antagonist protocol using hCG as trigger. It displays similar results, therefore it can be used as the first choice in patients at high risk for OHSS.

Selective modulation of the prostaglandin F2α pathway markedly impacts on endometriosis progression in a xenograft mouse model.

STUDY HYPOTHESIS: Selective activation or blockade of the prostaglandin (PG) F2α receptor (FP receptor) affects ectopic endometrial tissue growth and endometriosis development. STUDY FINDING: FP receptor antagonists might represent a promising approach for the treatment of peritoneal endometriosis. WHAT IS KNOW ALREADY: Eutopic and ectopic endometrium from women with endometriosis exhibit higher expression of key enzymes involved in the PGF2α biosynthetic pathway. It has also been shown that the PGF2α-FP receptor interaction induces angiogenesis in human endometrial adenocarcinoma. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: For this study, a mouse model of endometriosis was developed by inoculating human endometrial biopsies into the peritoneal cavity of nude mouse (n = 15). Mice were treated with AL8810 (FP receptor antagonist), Fluprostenol (FP receptor agonist) or PBS. Endometriosis-like lesions were collected and analysed for set of markers for angiogenesis, tissue remodelling, apoptosis, cell proliferation and capillary formation using qPCR and immunohistochemistry. MAIN RESULTS AND THE ROLE OF CHANCE: We found that selective inhibition of the FP receptor with a specific antagonist, AL8810, led to a significant decline in the number (P < 0.01) and size of endometriosis-like lesions (P < 0.001), down-regulated the expression of key mediators of tissue remodelling (MMP9, P < 0.05) and angiogenesis (VEGF, P < 0.01) and up-regulated the pro-apoptotic factor (Bax, P < 0.01) as compared with controls. Immunohistochemical analyses further showed a marked decrease in cell proliferation and capillary formation in endometrial implants from AL8810-treated mice, as determined by proliferating cell nuclear antigen (PCNA) and von Willebrand factor (vWF) immunostaining, respectively. Moreover, Fluprostenol, a selective FP receptor agonist, showed the opposite effects. LIMITATIONS, REASONS FOR CAUTION: We carried out this study in nude mice, which have low levels of endogenous estrogens which may affect the lesion growth. Caution is required when interpreting these results to women. WIDER IMPLICATIONS OF THE FINDINGS: This study extends the role of PG signalling in endometriosis pathogenesis and points towards the possible relevance of selective FP receptor antagonism as a targeted treatment for endometriosis. LARGE SCALE DATA: Not Applicable. STUDY FUNDING AND COMPETING INTERESTS: This work was supported by grant MOP-123259 to the late Dr Ali Akoum from the Canadian Institutes for Health Research. The authors have no conflict of interest.

Modifying the luteal phase support in natural cycle frozen-thawed embryo transfer improves cycle outcome.

With the recent trend toward single embryo transfer (ET), cryopreservation of extraneous embryos is becoming increasingly prevalent. Several replacement protocols for frozen-thawed ET (FET) exist, with no advantage of one protocol over the others. All consecutive patients undergoing natural cycle Day-3 FET cycles between May 2012 and March 2015 in our IVF unit were evaluated. While following spontaneous ovulation, all patients received progesterone luteal support. Since June 2014, patients underwent the same aforementioned natural cycle FET cycles, with two additional injections, one of recombinant hCG (250 mcg) and the other of GnRH-agonist (triptorelin 0.1 mg), on the day of transfer and 4 d later, respectively. While the patients' clinical characteristics, the prevalence of embryos that survived the thawing process and the number of embryos transferred were comparable between the earlier as compared with the later period, implantation rate, positive ß-hCG, clinical, and ongoing pregnancy rates were significantly higher during the later period. We, therefore, suggest that when natural cycle FET is offered, the addition of two injections of recombinant hCG and GnRH-agonist, on the day of transfer and 4 d later, respectively, might increase clinical pregancy rates. Further large prospective studies are needed to elucidate the aforementioned recommendation prior to its routine implementation.

Treatment of clinical endometritis in dairy cows by previously used controlled internal drug release devices.

Postpartum endometritis is considered as one of the diseases that lead to a potential profit reduction in dairy cows. The aims of the present study were to promote follicle growth by a previously used controlled internal drug release (CIDR) device and to evaluate its effect on the likelihood of recovery and the reproductive performance of clinical endometritis (CE) cows. Endometritis was diagnosed using ultrasonographic examination at 31 ± 3 (Day 0 of the experiment) days in milk, and CE cows were included in one of the three experimental groups according to the presence of a CL on their ovaries. Cows without CL on their ovaries received a reused CIDR device, which was previously used for 14 days (CIDR-14, n = 108), or PGF2α (PG-1, n = 112) on Day 0. In the third group, those with CL on their ovaries received PGF2α (PG-2, n = 107) at the same time. Ovarian structures, serum estradiol and progesterone concentrations were measured on Days 0, 7, and 14. Controlled internal drug release devices were removed, and response to treatment was evaluated in all treated cows on Day 14. Diameters of ovarian follicles were 11.61 ± 0.50, 12.46 ± 0.25, and 18.36 ± 0.60 mm on Day 7 and 11.63 ± 0.58, 14.35 ± 0.40, and 21.96 ± 0.77 mm on Day 14 in PG-1, PG-2, and CIDR-14 cows, respectively (P < 0.05). Serum estradiol concentrations were higher in CIDR-14 cows (141.17 ± 1.04 pg/mL) than in PG-1 (116.85 ± 1.05 pg/mL) and PG-2 (119.10 ± 1.05 pg/mL) cows on Day 7 (P < 0.05). Higher progesterone concentrations were observed in PG-2 cows than in PG-1 and CIDR-14 cows on Days 0, 7, and 14 (P < 0.001). The likelihood of clinical cure was 54.46%, 62.61%, and 64.81% in PG-1, PG-2, and CIDR-14 cows, respectively (P = 0.11). First-service conception risk, days to the first service, calving to conception interval, proportion of cows bred and pregnant by 120 days in milk did not differ among the treated groups (P > 0.05). The cumulative pregnancy risk was lower in PG-1 (77.67%) cows than in CIDR-14 (87.07%) and PG-2 (87.85%) cows (P = 0.02). In conclusion, reused CIDR would be contributed to the treatment of CE by promotion of follicle growth and induction of sustainable sources of endogenic estrogen secreted by the dominant follicle.

Ovarian Suppression With Triptorelin During Adjuvant Breast Cancer Chemotherapy and Long-term Ovarian Function, Pregnancies, and Disease-Free Survival: A Randomized Clinical Trial.

IMPORTANCE: Whether the administration of luteinizing hormone-releasing hormone analogues (LHRHa) during chemotherapy is a reliable strategy to preserve ovarian function is controversial owing to both the lack of data on long-term ovarian function and pregnancies and the safety concerns about the potential negative interactions between endocrine therapy and chemotherapy. OBJECTIVE: To evaluate long-term results of LHRHa-induced ovarian suppression during breast cancer chemotherapy. DESIGN, SETTING, AND PARTICIPANTS: Parallel, randomized, open-label, phase 3 superiority trial conducted at 16 Italian sites. Between October 2003 and January 2008, 281 premenopausal women with stage I to III hormone receptor-positive or hormone receptor-negative breast cancer were enrolled. Last annual follow-up was June 3, 2014. INTERVENTIONS: Patients were randomized to receive adjuvant or neoadjuvant chemotherapy alone (control group) or chemotherapy plus triptorelin (LHRHa group). MAIN OUTCOMES AND MEASURES: The primary planned end point was incidence of chemotherapy-induced early menopause. Post hoc end points were long-term ovarian function (evaluated by yearly assessment of menstrual activity and defined as resumed by the occurrence of at least 1 menstrual cycle), pregnancies, and disease-free survival (DFS). RESULTS: A total of 281 women (median age, 39 [range, 24-45] years) were randomized. Median follow-up was 7.3 years (interquartile range, 6.3-8.2 years). The 5-year cumulative incidence estimate of menstrual resumption was 72.6% (95% CI, 65.7%-80.3%) among the 148 patients in the LHRHa group and 64.0% (95% CI, 56.2%-72.8%) among the 133 patients in the control group (hazard ratio [HR], 1.28 [95% CI, 0.98-1.68]; P = .07; age-adjusted HR, 1.48 [95% CI, 1.12-1.95]; P = .006). Eight pregnancies (5-year cumulative incidence estimate of pregnancy, 2.1% [95% CI, 0.7%-6.3%]) occurred in the LHRHa group and 3 (5-year cumulative incidence estimate of pregnancy, 1.6% [95% CI, 0.4%-6.2%]) in the control group (HR, 2.56 [95% CI, 0.68-9.60]; P = .14; age-adjusted HR, 2.40 [95% CI, 0.62-9.22]; P = .20). Five-year DFS was 80.5% (95% CI, 73.1%-86.1%) in the LHRHa group and 83.7% (95% CI, 76.1%-89.1%) in the control group (LHRHa vs control: HR, 1.17 [95% CI, 0.72-1.92]; P = .52). CONCLUSIONS AND RELEVANCE: Among premenopausal women with either hormone receptor-positive or hormone receptor-negative breast cancer, concurrent administration of triptorelin and chemotherapy, compared with chemotherapy alone, was associated with higher long-term probability of ovarian function recovery, without a statistically significant difference in pregnancy rate. There was no statistically significant difference in DFS for women assigned to triptorelin and those assigned to chemotherapy alone, although study power was limited. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT00311636.

Comparison of ovulation induction protocols after endometrioma resection.

BACKGROUND AND OBJECTIVES: The aim of this study was to compare the in vitro fertilization (IVF) outcomes of long gonadotropin-releasing hormone agonist (GnRH-a) and GnRH-antagonist (GnRH-ant) protocols in endometriosis patients who have undergone laparoscopic endometrioma resection surgery. To our knowledge, there is no study in the current literature that compares the effectiveness of long GnRH-a and GnRH-ant protocols in management of IVF cycles in endometriosis patients who underwent laparoscopic endometrioma resection surgery. METHODS: Eighty-six patients with stage III to IV endometriosis who had undergone laparoscopic resection surgery for endometrioma were divided into 2 groups: those who had ovarian stimulation with a long GnRH-a protocol (n=44), and those who had ovarian stimulation with a GnRH-ant protocol (n=42). RESULTS: The number of follicles on human chorionic gonadotropin injection day, duration of hyperstimulation, number of retrieved metaphase II oocytes, and total number of grade 1 embryos were statically significantly higher in the long GnRH-a protocol. There were no significant differences in positive ß-human chorionic gonadotropin pregnancy rates (25% vs 21.4%; P=.269) and ongoing pregnancy rates per patient (20.5% vs 19.1%; P=.302) between the 2 protocols. CONCLUSIONS: Long GnRH-a and GnRH-ant protocols both present similar IVF outcomes in patients with endometriosis who have undergone laparoscopic endometrioma resection surgery. A long GnRH-a protocol may lead to a higher number of embryos that can be cryopreserved, providing the possibility of additional embryo transfers without having to go through the process of ovarian stimulation again.

Triptorelin for the treatment of endometriosis.

INTRODUCTION: Over the past 30 years, gonadotropin-releasing hormone agonists (GnRH-a) have been used to induce a hypoestrogenic status in women with endometriosis with the aim to cause an improvement in pain symptoms similar to that observed after menopause. Triptorelin is one of the most commonly used GnRH-a. AREAS COVERED: This review offers an explanation of the mechanism of action, of the pharmacokinetics and pharmacodynamics of triptorelin and gives the readers a complete overview of the studies on the clinical efficacy, tolerability and safety of this agent in patients with endometriosis. EXPERT OPINION: The studies reviewed in the current manuscript demonstrate the efficacy of triptorelin in improving pain symptoms caused by endometriosis. Further, this effect is confirmed by the reduction in the volume of the endometriotic nodules during treatment. Future research should evaluate whether the pre-operative administration of triptorelin prior to surgical excision of endometriomas may be useful in preserving the ovarian reserve.

Does cabergoline help in decreasing endometrioma size compared to LHRH agonist? A prospective randomized study.

AIM: The aim of this study was to compare the efficiency of dopamine agonist, Cabergoline, in decreasing the size of endometrioma, with that of luteinizing hormone releasing hormone (LHRH) agonist, triptorelin acetate. STUDY: This was a prospective, randomized study. SETTING: The setting was in two private medical centers in the UAE, from January 2011 to February 2012. PATIENTS AND METHODS: One hundred and forty patients complaining of endometrioma, and fulfilling the eligibility criteria, were chosen and divided into two groups as follows: Group I comprised 71 patients; all of them received Cabergoline tablets, 0.5 mg tablets, twice per week for 12 weeks. Group II comprised 69 patients; all of them received LHRH agonist, decapeptyl, 3.75 mg subcutaneous, single injection, once a month for 3 months. All patients underwent vaginal ultrasound before and after the treatment period to compare the change in the size of endometrioma by the same sonography team in each hospital that was blind to the treatment groups. OUTCOME: The outcome was measured by the changes in the endometrioma size by vaginal ultrasound after completion of the 3 months' treatment period. The management line was considered to be significantly effective if the endometrioma size was reduced by more than 25 % of its original pretreatment size. RESULTS: Group I: 46 out of the 71 patients (64.7 %) had significant decrease in endometrioma size. Group II: 15 out of 69 patients (21.7 %) had significant decrease in endometrioma size. Paired t test to compare the means of the two groups was highly significant (p < 0.05) CONCLUSION: Cabergoline (dostinex) yields better results in decreasing the size of endometrioma, compared to LHRH-agonist by exerting antiangiogenic effects through vascular endothelial growth factor receptor-2 (VEGFR-2) inactivation. It has no major side effects, easier to administer, and cheaper than LHRH agonists.