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.

Effect of GnRH agonist before IVF on outcomes in infertile endometriosis patients: a randomized controlled trial.

RESEARCH QUESTION: Does 3-months of gonadotrophin releasing hormone agonist (GnRHa) treatment before IVF improve clinical pregnancy rate in infertile patients with endometriosis? DESIGN: Single-blind, placebo-controlled clinical trial of 200 infertile women with endometriosis assigned to use GnRHa (study group) or placebo (control group) for 3 months before IVF. Clinical, embryological outcomes and stimulation parameters were analysed. Clinical pregnancy rate was the primary endpoint. In a subgroup of 40 patients, follicular fluid levels of oestradiol, testosterone and androstendione were measured. Gene expression profile of CYP19A1 was analysed in cumulus and mural granulosa cells. RESULTS: Implantation or clinical pregnancy rate were not significantly different between the two groups. Clinical pregnancy rates were 25.3% and 33.7% in the study and control groups, respectively (P = 0.212). Cumulative live birth rate was not significantly different: 22.0% (95% CI 13.0 to 31.0) in the study group and 33.7% (95% CI 24.0 to 44.0) in the control group (P = 0.077). Ovarian stimulation was significantly longer and total dose of gonadotrophins significantly higher in the study group (both P < 0.001). Serum oestradiol levels on the day of HCG were significantly lower in the study group (P = 0.001). Cancellation rate was significantly higher in the study group (P = 0.042), whereas cleavage embryos were significantly more numerous in the control group (P = 0.023). No significant differences in the expression of CYP19A1 gene in mural or cumulus granulosa cells or steroid levels in follicular fluid between the two groups were observed, but testosterone was significantly lower in the study group (P < 0.001). CONCLUSION: Three-months of GnRHa treatment before IVF does not improve clinical pregnancy rate in women with endometriosis.

The addition of single dose GnRH agonist to luteal phase support in artificial cycle frozen embryo transfer: a randomized clinical trial.

This prospective randomized clinical trial (RCT) was to evaluate the effect of single-dose gonadotrophin-releasing hormone agonist (GnRHa) in artificial cycle frozen-embryo transfer (AC-FET). A total of 868 FET cycles were included and randomized into two groups: Group A (n = 434) received GnRHa 0.1 mg subcutaneous injection on day 3 after embryo transfer (ET); Group B (n = 434) did not receive GnRHa. The demographic characteristics, primary endpoint (implantation rate) and secondary endpoints (chemical pregnancy rate, clinical pregnancy rate, ongoing pregnancy rate) were compared between two groups and subgroups (aged <35 years and 35-37 years). There were no significant differences in terms of the rates of implantation, clinical pregnancy, ongoing pregnancy, and miscarriage between two groups. While, the subgroups analysis showed the implantation rate was significantly increased in advanced age women (35-37 years) in GnRHa group compared with control group (45.3% vs. 27.8%, p = .03). In conclusion, single dose of GnRHa (0.1 mg triptorelin acetate) supplementation 3 days after ET in AC-FET cycles did not show significant benefit on pregnancy outcomes as a whole. However, in ageing women subgroup, the implantation rate was increasing by adding up GnRHa in peri-implantation periods, and this tendency needs to be further demonstrated by RCT with larger sample size.

Evaluation of different hormonal treatments on oestral and ovarian responses in Moroccan Beni Arouss goats during anoestrus and breeding season.

The efficacy of eight combinations of fluorogestone acetate (FGA, 20 or 40 mg as intravaginal device during 11 days), equine chorionic gonadotropin (eCG, 300 or 500 UI injected 48 hr before FGA removal) and prostaglandin F2α (cloprostenol, 0 or 50 µg injected 48 hr before FGA removal) aiming at induction and synchronization of oestrus and ovulation was evaluated during the anoestrus season in spring and during the breeding season in autumn in adult Beni Arouss goats. Oestrous behaviour was recorded between 12 and 60 hr after FGA removal. Blood samplings allowing to assess onset of the pre-ovulatory LH surge and increase of progesterone as sign of an active corpus luteum were performed, respectively, between 20 and 60 hr and 3, 5, 8 and 15 days after FGA removal. No season-related differences (spring vs. autumn) were observed for oestrous response (95% vs. 93%), pre-ovulatory LH surge (94% vs. 84%) and luteal response after 3-8 and 11-15 days post-treatment (respectively 92% vs. 66% and 92% vs. 98%). The onset of oestrus (21 [13-53] vs. 32 [12-54] hr) and LH surge (26 [20-60] vs. 38 [22-60] hr) occurred significantly later in autumn. FGA (40 vs. 20 mg) in autumn significantly delayed the onset of oestrus (36 [16-54] vs. 23 [12-47] hr) and LH surge (44 [26-58] vs. 33 [22-60] hr). Significant treatment-related differences were recorded for onset of LH surge (earliest for 20 mg FGA, 300 IU eCG, 50 µg PGF2α ) and onset of luteal phase (latest for 40 mg FGA, 300 IU eCG, 50 µg PGF2α ). In conclusion, the hormone combinations tested appeared equally effective in terms of oestrous and ovulation rates. Season has influenced significantly the onset of oestrus and LH surge, and the high dose regimen of FGA delayed the ovarian response in autumn.

A novel strategy for resynchronization of ovulation in Nelore cows using injectable progesterone (P4) and P4 releasing devices to perform two timed inseminations within 22 days.

We aimed to evaluate the reproductive performance of Nelore lactating cows submitted to a resynchronization 12 days after timed artificial insemination (TAI) with or without a long-acting progesterone (P4-LA) treatment. Nelore cows were submitted to a P4/oestradiol-based TAI protocol (D0 = insemination). On D12, cows in the control group (n = 184) received a new P4 intravaginal device (0.96 g), whereas cows in the P4-LA group (n = 192) received the P4 device and 75 mg P4-LA. Cows identified as non-pregnant (n = 120) by regression of corpus luteum using colour Doppler ultrasonography on D20 had the P4 device removed and received 500ug of sodium cloprostenol, 1 mg of oestradiol cypionate and 300 IU of eCG and were re-inseminated on D22. There was no difference (p > 0.10) in the pregnancy rate at D20, D30 and D60 after first TAI between the control (69%, 59.7% and 57%, respectively) and P4-LA (67%, 55.7%, and 55.2%, respectively) groups. Pregnancy losses were similar between both groups (p > 0.1). For cows submitted to the second TAI, the pre-ovulatory follicle size did not differ (p > 0.1), but the oestrous detection and pregnancy rates were greater (p < 0.05) in the P4-LA group (92.2% [59/64] and 60.9% [39/64], respectively) than in controls (75% [42/56] and 44.6% [25/56]). The cumulative pregnancy rate after two TAIs did not differ (p > 0.1) between control (73.3% [135/184]) and P4-LA (76% [146/192]) groups. The use of P4-LA at 12 days after TAI potentially increases the pregnancy rates for a new early resynchronization strategy associated with the Doppler imaging for pregnancy diagnosis and results in an alternative to perform two TAIs in 22 days in beef cows.

Intraoperative Effect of Preoperative Gonadotropin-Releasing Hormone Analogue Administration in Women Undergoing Cold Loop Hysteroscopic Myomectomy: A Randomized Controlled Trial.

STUDY OBJECTIVE: To evaluate the intraoperative effects of gonadotropin-releasing hormone (GnRH) analogue pretreatment in patients undergoing cold loop hysteroscopic myomectomy. DESIGN: Randomized controlled trial (Canadian Task Force classification I). SETTING: Arbor Vitae Center for Endoscopic Gynecology, Rome, Italy. PATIENTS: A total of 99 patients were randomized and subsequently allocated to the GnRH analogue group or to the nonpharmacologic treatment control group. Fifteen patients were lost after allocation, and 42 patients per group underwent hysteroscopic myomectomy. INTERVENTIONS: Cold loop hysteroscopic myomectomy. MEASUREMENTS AND MAIN RESULTS: The control group accomplished the treatment in a 1-step procedure more frequently than the GnRH analogue group (92.85% and 73.8% of cases, respectively; p = .040). The completion of the treatment was more unlikely in case of G2 myomas (p = .006), whereas no differences were recorded for G1 and G0 myomas. The multivariate analysis showed a significant correlation between the multiple-step treatment and the use of GnRH analogue (odds ratio, 5.365; 95% confidence interval [CI], 1.018-28.284; p = .048), grading (odds ratio, 4.503; 95% CI, 1.049-19.329; p = .043), and size of myomas (odds ratio, 1.128; 95% CI, 1.026-1.239; p = .013). CONCLUSIONS: Preoperative GnRH analogue administration did not facilitate the completion of cold loop hysteroscopic myomectomy in a single surgical procedure in G2 myomas and was correlated with a longer duration of the surgery. No significant benefits were found for G0 and G1 myomas. (ClinicalTrials.gov: NCT01873378.).

Use of two doses of cloprostenol in different intervals for estrus synchronization in hair sheep under tropical conditions.

This study evaluated the effect of two doses of prostaglandin at different intervals on reproductive parameters of crossbred ewes. In Experiment 1, 30 ewes received two doses of 120 µg cloprostenol at 7 (G 7 days), 9 (G 9 days), or 11.5 (G 11.5 days) days apart. Ultrasound assessments were performed from the first and second cloprostenol administration for 5 days or ovulation detection. Estrus signs were checked by a teaser male. Plasma progesterone concentration was measured before each cloprostenol dose. In Experiment 2, 95 ewes were allocated into the same treatments and after the second dose, ewes in estrus were mated. At 30 days after breeding, pregnancy diagnosis was conducted and prolificacy was evaluated at lambing. In Experiment 1, at the first cloprostenol administration, 50% of ewes had an active CL and all showed estrus. At the second administration, 66.7% of ewes had an active CL and one did not present estrus. There was no difference (P > 0.05) after the second dose for as follows: overall estrous response (90%), interval from cloprostenol administration to estrous onset (42.0 ± 4.9 h), estrus duration (31.5 ± 2.1 h), ovulation rate (100.0%), and number of ovulations (1.5 ± 0.3). In Experiment 2, both pregnancy and prolificacy rates were similar (P > 0.05) for G 7 days (73.3; 145%), G 9 days (75.9; 125%), or G 11.5 days (75.9; 145%), leading to an overall pregnancy rate of 75.0% (66/88) and prolificacy rate of 137%. Therefore, the three treatments proposed were able to promote high pregnancy and prolificacy rates in crossbred ewes.

Diagnostic utility of testosterone priming prior to dynamic tests to differentiate constitutional delay in puberty from isolated hypogonadotropic hypogonadism.

CONTEXT: Differentiation between constitutional delay in puberty (CDP) and isolated hypogonadotropic hypogonadism (IHH) during adolescence is a great clinical challenge, and the available diagnostic tests are of limited value. OBJECTIVE: To study the effect of withdrawal of short-term, low-dose testosterone therapy (testosterone priming) on the discriminatory power of dynamic tests for hypothalamo-pituitary-testicular axis to differentiate CDP from IHH. DESIGN: A prospective study (n = 30) consisting of 20 boys with delayed puberty (group A) and 10 patients with IHH (group B). INTERVENTION: Patients in groups A and B underwent Triptorelin and hCG stimulation tests, prior to and 2 months after withdrawal of 'testosterone priming' (100 mg intramuscularly 4 weekly for 3 months) and were followed up until the onset of puberty or 18 years of age, whichever was earlier. RESULTS: At baseline, Triptorelin-stimulated 4 h LH, with a cut-off of 2·8 IU/l, and hCG-stimulated day 7 testosterone with a cut-off of 3·8 nmol/l had sensitivities of 80% each, and specificities of 93% and 87%, respectively, to diagnose CDP. After withdrawal of testosterone, a 4 h LH cut-off of 14·7 IU/l and day 7 testosterone cut-off of 10·3 nmol/l had sensitivities of 93% and 88% respectively, and specificity and positive predictive value of 100% each. A basal inhibin B > 94·7 ng/l was discriminatory for diagnosing CDP after withdrawal of testosterone priming. CONCLUSIONS: Inhibin B levels or 4 h LH after Triptorelin stimulation are the best discriminatory tests to differentiate CDP from IHH, when performed after withdrawal of 'testosterone priming'.

Effect of mid-luteal phase GnRH agonist on frozen-thawed embryo transfers during natural menstrual cycles: a randomised clinical pilot study.

This prospective randomised crossover study evaluated the effect of mid-luteal single-dose gonadotropin-releasing hormone agonist (triptoreline) on pregnancy outcomes in natural-cycle frozen embryo transfers (FETs). Ninety-eight women were randomised to receive either standard luteal support with vaginal micronised progesterone or an additional single dose of 0.1 mg triptoreline at the time of implantation. The intervention group was composed of 65 FET cycles and the control group of 62 cycles. In the intervention group, there were more positive pregnancy tests, clinical pregnancies and live births, but the differences did not reach statistical significance. The mean beta human chorionic gonadotropin (ß-hCG) concentration of singleton pregnancies was significantly lower in the intervention group compared to the control group (p = 0.048). No difference was detected in the median birth weight of the newborns.

Which is the best IVF/ICSI protocol to be used in poor responders receiving growth hormone as an adjuvant treatment? A prospective randomized trial.

This open label randomized study aims to define the best protocol to be used with growth hormone in poor responders, with comparison performed to delineate which protocol offers the best cycle outcomes. Two-hundred eighty-seven poor responders were included. The patients were randomly allocated into four groups receiving growth hormone (GH) as an adjuvant therapy added to either long or short agonist protocol, miniflare or antagonist protocols. The short/GH gave significantly lower mean number of oocytes when compared with the long/GH, antagonist/GH and miniflare/GH (4 ± 1.69 versus 5.06 ± 1.83, 4.95 + / = 1.90 and4.98 ± 2.51, respectively p = 0.005). Considering the number of fertilized oocytes, the long/GH showed significantly higher levels than short/GH and antagonist/GH (3.73 ± 1.47 versus 3.02 ± 1.52 and 2.89 ± 1.14, respectively). The main drawback is that it required significantly higher HMG dose and longer duration of stimulation. The long/GH was superior when compared with the three protocols regarding the number of oocytes retrieved and fertilized. But, when considering the clinical pregnancy rates, there was a difference in favor of the long/GH but not reaching a statistically significant value (ClinicalTrials.gov Identifier: NCT01897324).

Corifollitropin alfa followed by hpHMG in GnRH agonist protocols. Two prospective feasibility studies in poor ovarian responders.

In two prospective uncontrolled feasibility trials, we examined the effect of corifollitropin alfa (CFA) followed by highly purified human menopausal gonadotrophin (hpHMG) in a short flare-up gonadotropin-releasing hormone (GnRH) agonist and a long GnRH agonist protocol for women with poor ovarian response. Overall, 45 patients were treated with short flare-up and 47 patients with the long agonist protocol. All patients received a single dose of 150 µg CFA, followed by 300 IU hpHMG 7 days later, triggering with 10 000 IU hCG, CSI and day 3 embryo transfer. Ongoing pregnancy rates (OPRs) did not differ between the short 15.6% and the long 17% agonist protocol (p = 0.85). Among patients treated with the short flare-up protocol, OPRs were 20% for younger patients (<40 years old) and 12% in older women (≥40 years old), p = 0.68. Similarly, in patients treated with the long agonist protocol younger women had an OPR of 26.7% versus 12.5% in older women, p = 0.23. Among patients treated with the short flare-up, live births rate were 15% and 4.3% for younger (<40 years old) and older patients (≥40 years old), respectively, p = 0.32. Similarly, in patients treated with the long agonist protocol, live births rate were 25% and 12.9% for younger (<40 years old) and older patients (≥40 years old), respectively, p = 0.41. None of the patients reported any serious adverse event related to treatment. According to our results, CFA followed by hpHMG in a short flare-up or long GnRH agonist protocol appears to be a feasible option for poor ovarian responders. Large phase III trials are mandatory prior to introduction in clinical practice.

A novel modified ultra-long agonist protocol improves the outcome of high body mass index women with polycystic ovary syndrome undergoing IVF/ICSI.

In an attempt to evaluate the effectiveness of a novel modified ultra-long agonist (ULA) protocol on polycystic ovary syndrome (PCOS) patients undergoing in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI), a retrospective study of 499 women employed with either ULA or conventional long agonist (LA) protocol was analyzed. In high BMI group (>25 kg/m²), the ULA protocol yielded significant higher clinic pregnancy rate (PR) (70.2% versus 50.8%, p < 0.05), implantation rate (52.7% versus 35.7%, p < 0.05) and live birth rate (63.8% versus 39.0%, p < 0.05) when compared with LA protocol. In low BMI group (≤25 kg/m²), the ULA protocol also demonstrated a higher clinic PR (70.8% versus 59.5%, p < 0.05) whereas implantation rate and live birth rate are comparable. Within ULA protocol, the clinic PR, implantation rate and live birth rate are similar between high and low BMI patients. Similarly, the clinic PR and live birth rate demonstrated no significant difference within LA group but there is a significant lower implantation rate (35.7% versus 63.9%, p < 0.05) observed in high BMI patients. No difference in miscarriage rate and severe OHSS rate was found among all groups. In conclusion, ULA protocol benefits the IVF outcomes of PCOS patients with high BMI status.

Risk of recurrent menorrhagia after hydrothermoablation: role of GnRH analogues neoadjuvant treatment in long-term successful rate.

OBJECTIVE: To evaluate the long-term effectiveness of presurgical therapy with GnRH analogues in patients who underwenthydrothermal endometrial ablation (HTA) for menorrhagia and assess the relationship between sonographically measured myometrium thickness and pelvic pain. MATERIALS AND METHODS: A prospective randomized control study comparing 15 women (Group A) with presurgical subcutaneous triptorelin depot injection before HTA with controls (Group B, n = 15). Inclusion criteria were: recurrent menorrhagia, uterus length < 12 cm, no previous hormonal therapy for at least six month, and family plan completed. Student's t test was applied, as appropriate, to compare continuous variables. Proportion were compared with chi-squared. RESULTS: After 12 months of follow-up, Group A showed a significantly lower (0% vs 20%; p = 0.03) failure rate after hydrothermoablation than the Group B and a generally higher successful rate at 24 and 48 months. The discomfort, evaluated with VAS, showed a mean value of 47.6 +/- 15.9 +/- SD); 96.7% of women reported a mild-moderate postoperative pain. No perioperative and late complications were recorded. CONCLUSIONS: Presurgical treatment with GnRH analogues seems to improve long-term efficacy of HTA. Perioperative pelvic pain seems to not be affected by myometrium thickness.

Short communication: estrus synchronization using progestogens or cloprostenol in tropical hair sheep.

The objective of the experiment was to compare the use of a PGF2α analogue (Cloprostenol) IM, with an intravaginal progestagen sponge, flurogestone acetate (FGA), and equine chorionic gonadotropin (eCG) IM application protocol. A total of 30 cyclical hair ewes (54.07 ± 0.5 kg live weight, body condition score 3.5 ± 0.5, and age 3 ± 1 years) were used. For the control group ewes (n = 15), intravaginal sponges (IS) impregnated with 20 mg of FGA were inserted for 12 days with 500 IU of eCG IM at sponges withdrawal. For the PG group ewes (Treatment group n = 15), two injections of Cloprostenol (75 mcg) were given 12 days apart. The presence of estrus was detected using two rams with 8 h interval beginning at the end of the treatment. Progesterone concentrations in blood were measured by solid phase radioimmunoassay. A student's t test was performed to analyze the duration of estrus and the interval between the ends of the treatment and the onset of estrus (ET-OE) presentation. Progesterone levels were compared with two-way ANOVA, with treatment, and day of menstrual cycle as fixed factors. Treatment costs ratio was calculated by dividing the total costs of FGA IS application between total costs of Cloprostenol application. Significant differences (P < 0.05) were found in the (ET-OE) interval and estrus duration. For the control group, estrus was presented at 30 + 8.2 h; in treatment group, at 44 h after the last application, duration of estrus was 54.9 + 8.34 h, and 41 + 1.83 h for the control and treatment group, pregnancy rates were 53.3 and 60.0 %, respectively. Significant differences (P < 0.001) were found from days 9 to 13 on Progesterone levels in both treatments. Treatment costs of Cloprostenol protocol were 2.63 cheaper than FGA including disposable material, biological products, and labor. It was concluded that Cloprostenol could be an effective tool in estrus synchronization in hair sheep in tropical areas.

GnRH-agonist ovulation trigger in patients undergoing controlled ovarian hyperstimulation for IVF with ultrashort flare GnRH-agonist combined with multidose GnRH-antagonist protocol.

OBJECTIVE: To evaluate, whether Gonadotropin-releasing hormone-agonist (GnRH-agonist or GnRH-ag) trigger in patients undergoing the ultrashort GnRH-ag/GnRH-antagonist (GnRH-ant) protocol is as effective as in patients at high risk to develop severe ovarian hyperstimulation syndrome (OHSS), who undergo the multidose GnRH-ant protocol. DESIGN: Cohort study. SETTING: University hospital. PATIENTS: All consecutive women aged ≤35 years admitted to our IVF unit from January 2011 to October 2011 who reached the ovum pick-up stage. INTERVENTIONS: Triggering final oocytes maturation by GnRH-ag instead of hCG, in high-responder patients undergoing either the ultrashort GnRH-ag/GnRH-ant or the multidose GnRH-antagonist controlled ovarian hyperstimulation (COH) protocols. MAIN OUTCOME MEASURES: Ovarian stimulation characteristics, percentage of mature oocytes, fertilization and pregnancy rates. RESULTS: No inbetween groups differences were observed in ovarian-stimulation related variable, percentage of mature oocytes, fertilization or pregnancy rates. No case of moderate-severe OHSS was reported in the study, or the control groups. CONCLUSIONS: Three consecutive doses of daily GnRH-ag administration at the beginning of ultrashort flare GnRH-ag/GnRH-ant COH protocol, did not interfere with the ability of the GnRH-ag to trigger final oocytes maturation at the end of the COH cycle.

Influence of the FecX(R) allele in heterozygous ewes on follicular population and outcomes of IVP and ET using LOPU-derived oocytes.

Ewes heterozygous for the FecX(R) allele (R+) in the bone morphogenetic protein 15 (BMP15) gene display increased ovulation rate and prolificacy. Besides this phenotypic advantage, the influence of the FecX(R) allele on follicle number and size, oocyte competence and in vitro production (IVP) remains undefined. With these aims, 8 R+ and 8 wild-type (++) ewes were subjected to 2 laparoscopic ovum pick-up (LOPU) trials (four sessions per trial; two with and two without FSH) and subsequent IVP and fresh embryo transfer. All follicles >3 mm were punctured (n = 1673). Genotype did not significantly affect the number of punctured follicles per ewe and session (10.4 and 10.2 in R+ and ++ untreated ewes, 17.4 and 14.3 in R+ and ++ FSH-treated ewes, respectively), but follicular diameter of R+ ewes was significantly reduced compared with ++ ewes (-0.2 mm in untreated and -0.8 mm in FSH-treated ewes; p < 0.01). R+ ewes showed higher recovery rate and increased numbers of total and suitable cumulus-oocyte complexes for in vitro maturation (IVM). Similar rates of day 8 blastocysts were observed in R+ (36.1%, 147/407) and ++ (32.6%, 100/307) ewes, but the final output of day 8 blastocysts per ewe and session was higher in R+ ewes (+0.75; p < 0.005), without differences in survival rate at birth of the transferred embryos (40.4%, 21/52 vs 36.4%, 16/44, respectively). In conclusion, a higher number of oocytes proven to be competent for in vitro development and embryo survival after transfer are recovered from R+ ewes, despite the lower mean size of their follicles at puncture.

Plasma clearance and half-life of prostaglandin F2alpha: a comparison between mares and heifers.

Horses are about five times more sensitive to the luteolytic effect of prostaglandin F2alpha (PGF) than cattle, as indicated by a recommended clinical dose of 5 mg in horses and 25 mg in cattle. Novel evaluations of the PGF plasma disappearance curves were made in mares and in heifers, and the two species were compared. Mares and heifers (n = 5) of similar body weight were injected (Min 0) intravenously with PGF (5 mg per animal). Blood was sampled every 10 sec until Min 3, every 30 sec until Min 5, every 10 min until Min 60, and every 30 min until Min 240. The mean PGF concentration was greater (P < 0.05) in mares than in heifers at Min 1 through Min 60 and at Mins 180 and 240. The mean time to maximum PGF concentration was not different between mares (42.0 ± 8.6 sec) and heifers (35.0 ± 2.9 sec). The apparent plasma clearance, distribution half-life, elimination half-life, and maximum plasma PGF concentration were 3.3 ± 0.5 L h(-1) kg(-1), 94.2 ± 15.9 sec, 25.9 ± 5.0 min, and 249.1 ± 36.8 ng/ml, respectively, in mares and 15.4 ± 2.3 L h(-1) kg(-1), 29.2 ± 3.9 sec, 9.0 ± 0.9 min, and 51.4 ± 22.6 ng/ml, respectively, in heifers. Plasma clearance was about five times less (P < 0.0005), maximum plasma PGF concentration was five times greater (P < 0.002), and the distribution half-life and elimination half-life were about three times longer (P < 0.005) in mares than in heifers. The fivefold greater plasma clearance of PGF in heifers than in mares corresponds to the recommended fivefold greater clinical dose of PGF in cattle and supported the hypothesis that the metabolic clearance of PGF is slower in mares than heifers.

Effects of d-cloprostenol dose and corpus luteum age on ovulation, luteal function, and morphology in nonlactating dairy cows with early corpora lutea.

Luteolysis is a key event in cattle reproduction. A standard dose of exogenous PGF(2α) will induce full luteolysis in the majority of cows with a matured corpus luteum (CL). However, this will not occur in cows with a CL <5d old. To date, it is not known whether a larger dose will have a more potent luteolytic effect in cows during early diestrus. The objective of this study was to characterize the effect of 2 doses of d-cloprostenol (150 and 300 µg) on the progesterone concentration, luteal diameter, and ovulation rate in nonlactating dairy cattle 96 to 132 h postovulation. Twenty nonlactating dairy cows were included in the study. Each cow received 2 treatments of d-cloprostenol in 2 consecutive cycles: a standard dose of 150 µg and a double dose of 300 µg. The cows were allocated randomly to 1 of 4 groups (5 cows in each group) according to the age of the CL at the time of treatment: 96, 108, 120, and 132 h. The exact time of ovulation was known within 12h, because of twice per day ultrasound examination. The CL diameter and progesterone concentration were measured before treatment (d 0) and 2 and 4d after treatment. Within each CL age group, the effect of d-cloprostenol dose on luteolysis was determined. More cows treated with double dose tended to have full luteolysis compared with the standard dose (8/10 vs. 4/10, respectively). This effect was only apparent in cows with CL of 120 and 132 h but not in earlier CL. The interval from treatment to ovulation was shorter (3.3 ± 0.1d) in cows treated with a double dose than in cows treated with the standard dose (4.5 ± 0.4d).

Ovarian response to oestrous synchronization protocol based on use of reduced doses of cloprostenol in cyclic goats.

The objective of this study was to assess the efficacy of two reduced doses vs a high/luteolytic dose of cloprostenol on luteolytic activity and synchronization of oestrus in cyclic goats. Experiment 1, included 24 goats randomly allocated to three groups: control group (group H) received a single high dose of cloprostenol (87.5 µg; 1.0 ml; i.m.) and M and L groups, which received half (43.75 µg; 0.5 ml) and a third (26.25 µg; 0.3 ml) of the highest dose, respectively. Experiment 2, included 24 goats randomly assigned to the same experimental groups. Each group was treated using two injections of cloprostenol administered 10 days apart to synchronize oestrus. Transrectal ultrasonographic scanning (US) was performed to detect the presence, size and development of corpora lutea and ovarian follicles. Furthermore, detection of oestrus was performed every 12 h between 24 and 72 h after the second injection of cloprostenol, and the luteolytic effect was verified by US. In Experiment 1, all goats that had corpora lutea at timing of treatment regressed their corpora lutea. In Experiment 2, the occurrence of oestrus and the interval between treatment to onset of oestrus were: 100%, 49.5 ± 3.0 h; 100%, 51.0 ± 3.0 h; and 75%, 56.0 ± 3.5 h for H, M and L groups, respectively. The development of preovulatory follicles and occurrence of subsequent corpora lutea were similar among groups. In summary, the use of 26.25 µg of cloprostenol is effective for the synchronization of oestrus in cyclic goats.

The effect of systemic administration of cloprostenol on ovulation in mares treated with a prostaglandin synthetase inhibitor.

Prostaglandins (PGs) are essential to trigger the cascade of events that degrade the extracellular matrix of follicles leading to follicular rupture and ovulation. In mares, systemic administration of flunixin meglumine (FM), a PG synthetase inhibitor, blocks ovulation by inducing luteinized unruptured follicles (LUF). In the rat, the administration of PGF(2α) (PGF) and PGE restored ovulation in indomethacin treated animals. The mares were treated with FM 0, 12, 24 and 36 h after human chorionic gonadotrophin (hCG) administration to induce experimentally LUF (n = 15) or were left untreated (controls, n = 5). In addition, 250 µg of cloprostenol were administered intravenously to the mares 33, 35 and 36 h (CLO 33, n = 5) or 48, 49 and 50 h (CLO 48, n = 5) after hCG. One group was treated with FM but not with cloprostenol (FM-control, n = 5). The ovulation rate, follicular diameter and progesterone concentration were compared amongst groups. The ovulation rate at 48 h was higher (p < 0.05) in the controls (100%) than in the FM-control (0%), CLO 33 (0%) or CLO 48 (20%) mares. All but one FM treated mares developed LUF by 48 h after hCG administration. Two LUF collapsed between 48 and 60 h and 72 and 84 h in one mare from FM-control and from the CLO 33 group each, respectively. Progesterone concentration was significantly higher (p < 0.05) in the control mares than in any of the FM treated mares 5, 9 and 13 days after hCG. In conclusion, FM administered during the periovulatory period blocked ovulation in the mares. In contrast, the administration of cloprostenol, a PGF analogue, in the previously FM treated mares failed to restore ovulation.