Symptom control after different duration of triptorelin treatment following conservative surgery for deep infiltrating endometriosis: Post-hoc analysis of a multicentre, prospective, real-world study.

ABSTRACT: Triptorelin has been used after surgery in deep infiltrating endometriosis. This post-hoc analysis aimed to evaluate symptom control between patients receiving 1-3 triptorelin injections and those receiving 4-6 injections within 24 months of conservative surgery for deep infiltrating endometriosis, in the real-world.Included patients were divided into two groups (received up to 3 months injections in group A, 4-6 injections in group B) based on the numbers of triptorelin (Diphereline, 3.75 mg intramuscular injection once every 28 days for up to 24 weeks) administration. Evolution in score of pain intensity at 3, 6, 9, 12, 18, and 24 months after primary triptorelin administration and symptom improvement/recurrence rates between two groups were compared. Symptoms of pain intensity were assessed using a visual analogue scale (VAS) with a range from 0 to 10 cm. An improvement in symptoms was defined as a reduction of at least 3 cm or 3 units from pre-surgery levels.156 patients in group A and 228 in group B. Pain symptom score (mean ±â€Šstandard deviation) diminished to a nadir at 3-months for group A and 6-months for group B; at 6-months nadir scores were significantly lower in group B (0.9 ±â€Š1.7 vs 0.4 ±â€Š1.2 respectively, P = .002). No significant difference for pain symptom scores between both groups at 24-months (P = .269). The 6-month and 24-month cumulative improvement rates of pain (80.6% vs 89.8%, P = .014 and 82.6% vs 90.7%, P = .025) and gastro-intestinal symptoms (61.0% vs 80.8%, P = .022 and 61.0% vs 83.3%, P = .008) were significantly higher in group B, whereas there was no significant difference in rates of menstrual disorders and urinary symptoms. There is no significant difference for 12-months and 24-months cumulative recurrence rates of total symptoms between both groups (11.3% vs 13.8%, P = .568 and 16.1% vs 26.0%, P = .094).In women with deep infiltrating endometriosis, longer treatment with triptorelin following conservative surgery was associated with a decrease in symptom intensity and greater improvement of pain symptoms in the short-term and greater improvement of gastro-intestinal symptoms in the long-term.Trial registration number: ClinicalTrials.gov, NCT01942369.

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.

Cloprostenol, a synthetic analog of prostaglandin F2α induces functional regression in cultured luteal cells of felids†.

In the present study, we investigated the effect of the synthetic analog of prostaglandin F2α (PGF2α)-cloprostenol-on cultured steroidogenic luteal cells of selected felid species over a 2-day culture period. The changes induced by cloprostenol were measured based on progesterone concentration and mRNA expression analysis of selected genes. Cloprostenol significantly reduced concentration of progesterone in cell culture medium of small luteal cells isolated from domestic cat corpora lutea (CL) at the development/maintenance stage (P < 0.05), but did not influence progesterone production in cultured cells from the regression stage. A decrease or complete silencing of progesterone production was also measured in cultured luteal cells of African lion (formation stage) and Javan leopard (development/maintenance stage). Gene-expression analysis by real-time PCR revealed that treatment with cloprostenol did not have an influence on expression of selected genes coding for enzymes of steroidogenesis (StAR, HSD3B, CYP11A1) or prostaglandin synthesis (PTGS2, PGES), nor did it effect hormone receptors (AR, ESR1, PGR, PTGER2), an anti-oxidative enzyme (SOD1) or factors of cell apoptosis (FAS, CASP3, TNFRSF1B, BCL2) over the studied period. Significant changes were measured only for expressions of luteinizing hormone (P < 0.05), prolactin (P < 0.05) and PGF2α receptors (P < 0.005) (LHCGR, PRLR, and PTGFR). The obtained results confirm that PGF2α/cloprostenol is a luteolytic agent in CL of felids and its impact on progesterone production depends on the developmental stage of the CL. Cloprostenol short-term treatment on luteal cells was associated only with functional but not structural changes related to luteal regression.

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.

Transcriptome analysis of sheep follicular development during prerecruitment, dominant, and mature stages after FSH superstimulation.

Sheep is usually a monovular animal; superovulation technology is used to increase the number of offspring per individual and shorten generation intervals. To date, mature FSH superstimulatory treatments have been successfully used in sheep breeding, but much remains unknown about genes, pathways, and biological functions involved in follicular development. Therefore, in this study, we performed transcriptome profiling of small follicles (SFs; 2-2.5 mm), medium follicles (MFs; 3.5-4.5 mm), and large follicles (LFs; > 6 mm) in Mongolian ewes after FSH superstimulation. Furthermore, we identified differentially expressed genes and performed Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology enrichment analyses in 3 separate pairwise comparisons. We found that ovarian steroidogenesis was significantly enriched in the SFs versus MFs analysis; the associated genes, cytochrome P450 family 19 (CYP19) and Hydroxy-delta-5-steroid dehydrogenase 3 beta- and steroid delta-isomerase 1 (HSD3B1), were significantly upregulated. Moreover, proline metabolism, glutathione metabolism, and PPAR signaling pathways were significantly enriched in the LFs versus SFs analysis; the associated genes, glutamate-cysteine ligase modifier subunit (GCLM) and cystathionine gamma-lyase (CTH), were significantly upregulated, whereas peroxisome proliferator-activated receptor gamma (PPARγ) was significantly downregulated. In summary, our study provides basic data and possible biological direction to further explore the molecular mechanism of sheep follicular development after FSH superstimulation.

Luteotropic effects of human chorionic gonadotropin administered 7.5 days after synchronous estrous induction in Morada Nova ewes.

This study was conducted in ewes to assess effects of human chorionic gonadotropin (hCG) administration after imposing an estrous induction treatment regimen. Ewes (n = 115) were treated with a 60 mg medroxyprogesterone-intravaginal-sponge for 6 d plus 200 IU of equine chorionic gonadotropin (eCG) im and 37.5 µg d-cloprostenol im 36 h before sponge removal (Day 0). After natural mating, ewes having at least one corpus luteum (CL; n = 108) were administered either 1 mL of saline (G-Control; n = 53) or 300 IU of hCG (G-hCG; n = 55) on Day 7.5 after sponge removal (Day 0). Ovarian ultrasonography and blood collection were performed on Days 7.5, 13.5, 17.5, 21.5, and 30.5. Accessory CL (aCL) were observed in 81.5 % (G-hCG) and 0.0 % (G-Control) of ewes (P = 0.0001). Diameter, area, and volume of luteal tissue were greater (P < 0.05) in G-hCG from Day 13.5 to 30.5. Progesterone (P4) concentrations were greater (P < 0.05) on Days 13.5, 17.5, 21.5 and 30.5 for ewes of the G-hCG group. Pregnancy percentage was similar (P = 0.25) between groups [47.1 % (G-control) compared with 60.0 % (G-hCG)], although total number of lambs produced by estrous synchronized ewes was greater (P = 0.005) in ewes of the G-hCG group (90.9 % compared with 66.0 %). In conclusion, hCG administration 7.5 days after sponge removal from Morada Nova ewes during the non-breeding season is an effective treatment to induce aCL formation, improve luteal tissue biometry and P4 concentrations, and to enhance the total number of lambs born.

Endocrine Requirements for Oocyte Maturation Following hCG, GnRH Agonist, and Kisspeptin During IVF Treatment.

Objective: The maturation of oocytes to acquire competence for fertilization is critical to the success of in vitro fertilization (IVF) treatment. It requires LH-like exposure, provided by either human chorionic gonadotropin (hCG), or gonadotropin releasing hormone agonist (GnRHa). More recently, the hypothalamic stimulator, kisspeptin, was used to mature oocytes. Herein, we examine the relationship between the endocrine changes following these agents and oocyte maturation. Design: Retrospective cohort study. Methods: Prospectively collected hormonal data from 499 research IVF cycles triggered with either hCG, GnRHa, or kisspeptin were evaluated. Results: HCG-levels (121 iU/L) peaked at 24 h following hCG, whereas LH-levels peaked at ~4 h following GnRHa (140 iU/L), or kisspeptin (41 iU/L). HCG-levels were negatively associated with body-weight, whereas LH rises following GnRHa and kisspeptin were positively predicted by pre-trigger LH values. The odds of achieving the median mature oocyte yield for each trigger were increased by hCG/LH level. Progesterone rise during oocyte maturation occurred precipitously following each trigger and strongly predicted the number of mature oocytes retrieved. Progesterone rise was positively associated with the hCG-level following hCG trigger, but negatively with LH rise following all three triggers. The rise in progesterone per mature oocyte at 12 h was greater following GnRHa than following hCG or kisspeptin triggers. Conclusion: The endocrine response during oocyte maturation significantly differed by each trigger. Counter-intuitively, progesterone rise during oocyte maturation was negatively associated with LH rise, even when accounting for the number of mature oocytes retrieved. These data expand our understanding of the endocrine changes during oocyte maturation and inform the design of future precision-triggering protocols.

Addition of eCG to a 14 d prostaglandin treatment regimen in sheep FTAI programs.

In the present study, there was evaluation of the alternative of adding eCG as part of a long-interval prostaglandin-F2α (PG) treatment on the reproductive efficiency of Merino sheep during the breeding season. A total of 210 ewes and 182 ewe lambs were randomly assigned to three experimental groups to induce the timing of estrus among ewes in a: Long-interval PG, group being synchronized using two doses of PG 14 days apart; Long-interval PG + eCG group being synchronized using the same treatment regimen as Group PG with the addition of 200 IU eCG to the regimen, administered concomitantly with the second PG administration; and MAP + eCG group being synchronized with intravaginal progestin sponges for 14 days plus 200 IU eCG, administered at the time of sponge removal. The percentage pregnancy rate in ewes of the MAP + eCG group was greater than the ewes of the Long-interval PG and Long-interval PG + eCG groups (76.4 % compared with 52.0 % and 62.5 %, respectively; P < 0.05). The prolificacy rate was greater in the ewes of the Long-interval PG+eCG group compared with the other groups (114 % compared with 100 % and 103 %, respectively; P < 0.05). When considering the fecundity rate, ewes of the Long-interval PG+eCG and MAP+eCG groups had greater values than ewes of the Long-interval PG group (71.2 % and 78.8 % compared with 52.0 %, respectively; P < 0.05). The Long-interval PG+eCG is an alternative to the conventional progestin sponge plus eCG treatment regimen with there being a greater fecundity rate when this regimen is used compared with the Long-term PG and similar to MAP-eCG treatment regimens.

Effects of follicular ablation and GnRH on synchronization of ovulation and conception rates in embryo recipient heifers.

Two experiments were performed to determine effects of follicular ablation (FA) and GnRH treatment on conception rate and synchronization in timing of ovulation among Holstein heifers. In Experiment 1, heifers were randomly allocated to four groups: Control (n = 84): prostaglandin F2α (PGF) IM on Day 0; FA-5/GnRH (n = 43): FA 5 days before PGF and GnRH on Day 2; FA-4/GnRH (n = 48):FA 4 days before PGF and GnRH on Day 2; andFA-3/GnRH (n = 21): FA 3 days before PGF and GnRH on Day 2. Ultrasonography was performed to determine follicular size, ovulation occurrence, and size of CL. In Experiment 2, heifers were assigned to three groups: Control (n = 264), FA-5/GnRH, and FA-4/GnRH. Pregnancy diagnosis was performed at Days 30 and 60. In Experiment 1, size of largest follicle at time of PGF was less variable (P ≤ 0.05) in all FA groups compared to the Control group. With the FA-5/GnRH and FA-4/GnRH treatments, there were greater (P ≤ 0.05) proportions of timing of ovulation synchronization (86 % and 85 %, respectively) compared to the Control (61 %) and FA-3/GnRH (62 %) groups. In Experiment 2, conception rates did not differ among groups, however, there were more pregnancies per cow when timing-of-ovulation treatments were imposed. In conclusion, follicular ablation combined with GnRH treatment resulted in an increased proportion of heifers having synchronized ovulation and, therefore, number of recipient heifers available for embryo transfer. Additionally, there was no effect on conception rate when there was greater synchronization in timing of ovulation among heifers.

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.

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.

GnRHa for trigger and luteal phase support in natural cycle frozen embryo transfer - A proof of concept study.

We aimed to explore whether ovulation induced by a GnRH analogue (GnRHa), followed by daily GnRHa luteal support provides an efficient platform for natural cycle frozen embryo transfer (NC-FET). In this cohort study, included were normo-ovulatory women who underwent NC-FET cycles, under the age of 40, with an antral follicle count > eight. Ovulation was triggered with triptorelin (0.2 mg Decapeptyl; Ferring), and luteal support was initiated two days later, using a Nafarelin inhaler (Synarel, Pfizer), 200 µg twice daily. Main outcome measures were luteal estradiol and progesterone levels (three to five days following ovulation), implantation rate, ongoing pregnancy rate, early pregnancy loss rate, and live birth rate. Fifty-one patients treated between 2017 and 2018 were included. Mid luteal progesterone levels among study patients, were non-significantly different between patients who achieved pregnancy and those who did not, but differed significantly on day 14 following ovulation (86.0 ± 31.3 vs. 9.8 ± 9.5 nmol/L, respectively, p < 0.001). Twenty-three patients achieved a clinical pregnancy (45.1 %); interestingly, there were no chemical pregnancies. Three pregnancies ended in an early abortion at 6-7 weeks gestation, and 20 pregnancies continued as ongoing pregnancies (39.2 %). One patient had a late abortion at 16 weeks gestation, and 14 had a live birth. In conclusion, in this proof of concept study, inducing ovulation with a bolus of GnRHa in NC-FET, followed by repeated daily GnRHa administration, resulted in satisfactory luteal phase steroid levels and high ongoing pregnancy and live birth rates.

Transcervical vs. laparotomy embryo collection in ewes: The effectiveness and welfare implications of each technique.

This study assessed animal welfare in ewes subjected to transcervical (TC) or laparotomy (LP) embryo collection, and the efficiency of these two techniques. Santa Inês ewes (n = 57) received a protocol for estrus synchronization and superovulation. Cervical dilation protocol was initiated 12 h before embryo collection in all ewes. Depending on the success of cervical passage, the embryos were collected from ewes by either TC or LP. Records were made of physiological (rectal temperature (RT) and heart rate (HR)), endocrine (cortisol concentration), biochemical (glycaemia, total proteins, globulin and albumin concentrations), and behavioral variables. Data were recorded before fasting (BF) and sedation (BS), during (DC) and immediately after embryo collection (IAC), and 1 h (1hAC), 3 h (3hAC), 6 h (6hAC), 12 h (12hAC), 24 h (24hAC), and 48 h (48hAC) after embryo collection. The LP and TC procedures were applied to 22 and 35 ewes (with 100.0% and 94.3% of procedures being successful, respectively). The use of LP took longer than TC (P = 0.007) but was less effective in the recovery of uterine fluid and structures (P = 0.0002 and P = 0.0180, respectively), with no difference in the number of viable embryos recovered per animal. The TC procedure induced a greater RT at DC (P = 0.002) and IAC moments (P < 0.0001). The heart rate was greater in TC than LP in IAC (P = 0.036). On the other hand, HR was greater with LP at 12hAC (P = 0.033) and 24hAC (P = 0.002). There was no interaction between the procedures and time on total proteins, albumin, or globulin concentrations. The TC procedure induced greater glycaemia than LP in IAC (P < 0.0001). LP induced greater serum cortisol concentration than TC at DC, IAC, 1hAC (P = 0.0004; P = 0.0006; P = 0.036, respectively), even though it was greater in the TC than the LP procedure at 3hAC (P = 0.008). In conclusion, the TC embryo collection was more effective than the traditional LP procedure. Although both embryo collection procedures affected ewes' welfare, the TC procedure is probably less stressor than the LP.

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.

Early resynchronization of non-pregnant beef cows based in corpus luteum blood flow evaluation 21 days after Timed-AI.

The study aimed to verify whether a hormone protocol started at Day 13 (D13) after Timed Artificial Insemination (TAI) influences the conception rate. Nelore cows (primiparous and multiparous) from two commercial beef farms (n = 1,431) were first TAI (D0). Timed AI was performed in lots (TAI Lots) ranging from 187 to 346 cows. On D13, regarding the TAI lot, cows were assigned for either receiving (Resynch group, n = 1,002) or not (Control group, a subset of approximately 30%, n = 429) another hormone protocol for resynchronization. The same hormone protocol was used for the first TAI and for the resynchronization, except for 1 mg instead of 2 mg of estradiol benzoate (EB) at the begging of the protocol. Eight days later (D21), the Resynch group was checked for corpus luteum blood flow by color Doppler ultrasonography, and in those detected as non-pregnant, the protocol was completed and a 2nd TAI was performed at D23. Pregnancy diagnosis was later (D30) performed by B-mode ultrasonography in the control group and confirmed in the presumptive pregnant cows from the 1st TAI of the Resynch group. The remaining cows were checked for pregnancy 30 days after the 2nd TAI (experimental Day 53). The statistical model to explain conception rate considered the effects of Group (Control or Resynch), Farm, Parity (primiparous or multiparous), Sire, Technician (who perform AI), TAI Lot and pertinent interactions (Group*Parity, Group*Farm and Group*TAI Lot). The statistical analyses of the model were performed using the Proc Glimmix (SAS virtual University Edition). The conception rate for the 1st TAI was similar (P > 0.4) between Control (50.3%, 216/429) and Resynch group (52.6%, 527/1002). The positive predictive diagnostic on D21 showed high relation with PD30 (90.7%, 527/581). In Resynch group, non-pregnant cows (n = 421, 1002 minus 581) were re-inseminated. The conception rate of the 2nd TAI (42.8%, 180/421) was affected (P < 0.002) by side effects of the Farm (48.5 vs. 33.1%) and Parity (51.2 vs. 40.3%, for multiparous vs. primiparous, p < 0.001). Nevertheless, after the 2 TAIs of the Resynch group, the cumulative conception rate was 70.5% (707/1002). In conclusion, the early resynchronization of cows with a low (1 mg) EB dose and progesterone device at D13 after TAI can be used as a strategy to reduce conception interval in beef cattle, and thus to increase the number of pregnant cows from artificial insemination after the breeding season.

Progesterone-based timed AI protocols for Bos indicus cattle II: Reproductive outcomes of either EB or GnRH-type protocol, using or not GnRH at AI.

The aim of these experiments was to study ovarian dynamics and fertility of Bos indicus beef cattle submitted to 7-d progesterone (P4)-based fixed-time AI (FTAI) protocols using different hormonal treatments. In Exp. 1, 2 yr old Nelore heifers (n = 973) were randomly assigned to one of four treatments: EB-0 (estradiol benzoate, EB on D0 and no GnRH at AI), EB-G (EB on D0 and GnRH at AI), G-0 (GnRH on D0 and no GnRH at AI), or G-G (GnRH on D0 and at AI). On D0, heifers received an intravaginal P4 implant (0.5 g) for 7 d and EB (1.5 mg) or GnRH (16.8 µg). On D7, the P4 implant was withdrawn and heifers received cloprostenol (PGF; 0.5 mg) and estradiol cypionate (EC, 0.5 mg). Heifers in G groups also received PGF and eCG (200 IU) on D6, whereas EB heifers received eCG on D7. At FTAI on D9, only EB-G and G-G groups received GnRH (8.4 µg). In Exp. 2, Nelore cows (n = 804) received the same treatments (EB-0, EB-G, G-0, or G-G) using a 1.0 g P4 implant, 2.0 mg EB, and 300 IU eCG. Effects were considered significant when P ≤ 0.05. After treatment on D0, G had more ovulations than EB in heifers (60.3 [287/476] vs. 12.7% [63/497]) and cows (73.7 [83/112] vs. 24.4% [28/113]). Luteolysis after D0 was greater in EB than G in heifers (39.2 [159/406] vs. 20.0% [77/385]) and cows (25.5 [14/55] vs. 1.6% [1/64]). Heifers in G had larger follicles (mm) than EB on D7 (10.3 ± 0.2 vs. 9.2 ± 0.2) and at AI (11.9 ± 0.2 vs. 11.3 ± 0.2). Cows had larger follicles in G than EB on D7 (11.0 ± 0.3 vs. 9.9 ± 0.3) but not at AI. More estrus was observed in G than EB for heifers (80.3 [382/476] vs. 69.6% [346/497]) and cows (67.6 [270/400] vs. 56.2% [227/404]). There was no interaction between D0 and D9 treatments on pregnancy per AI (P/AI) in heifers (EB-0: 56.7 [139/245], EB-G: 53.6 [135/252], G-0: 52.6 [127/241], and G-G: 57.5% [135/235]). However, cows from EB-G had greater P/AI than EB-0 (69.5 [142/204] vs. 60.2% [120/200]), whereas P/AI for G-0 (62.7% [127/203]) was similar to G-G (60.9% [120/197]). In heifers, there was no interaction of GnRH at AI with estrus, however, cows that did not display estrus had greater P/AI if they received GnRH at AI (GnRH = 59.1 [91/154] vs. No GnRH = 48.2% [78/162]). Thus, protocols initiated with EB or GnRH for Bos indicus heifers and cows had differing ovarian dynamics but similar overall fertility, enabling their use in reproductive management programs. Treatment with GnRH at time of AI increased fertility in some instances in Bos indicus cows but not in heifers.

Fertility of Women Treated during Childhood with Triptorelin (Depot Formulation) for Central Precocious Puberty: The PREFER Study.

BACKGROUND: Gonadotropin-releasing hormone analogues (GnRHa) administered as depot formulations are the standard of care for children with central precocious puberty (CPP). Puberty resumes after treatment discontinuation, but little is known concerning fertility in women who have been treated with GnRHa for CPP during childhood. METHODS: The PREFER (PREcocious puberty, FERtility) study prospectively analysed fertility, via a series of questionnaires, in women treated during childhood with triptorelin (depot formulation) for CPP. Co-primary endpoints were the proportion of women wanting a pregnancy any time before study inclusion and during the follow-up period but not pregnant 6 and 12 months after stopping contraception and the waiting time to pregnancy (WTP). RESULTS: A total of 574 women were identified, and 194 women were included in the analysis. Although there were not enough data for primary endpoint assessment, few women (1.7%) reported issues with fertility or were unable to become pregnant despite trying to conceive. Most pregnancies (84.4%, 95% CI [67.2-94.7%]) occurred within 1 year of trying to conceive, in line with the WTP for women without previous CPP. CONCLUSION: The results, based on a limited sample of patients, suggest that CPP treated with triptorelin does not negatively impact women's fertility in adulthood. These results need to be consolidated with a subsequent study performed when these women will have reached their mid-thirties.

Uterine hemodynamics during a short-term progesterone synchronization protocol in ewes.

Twenty-eight pluriparous and non-lactating Santa Inês sheep were synchronized with vaginal sponge and an intramuscular (IM) injection of 37.5 µg of cloprostenol on random days of the estrous cycle (D0); day 6 (D6), at 7:00 am, the devices were removed, and after 24 h (D7), GnRH analog (25 µg of lecirelin) was administrated. Fixed-time artificial insemination (FTAI) with cervical traction by the transcervical route was performed 52 to 58 h after sponge removal. Doppler velocimetry of both uterine arteries was performed on D0, D2, D4, and the morning of D6 (every 48 h), and then every 12 h from D6 to D8 (7:00 a.m. and 7:00 p.m.). We analyzed the peak systolic velocity (PSV), end-diastolic velocity (EVD), time-averaged maximum and mean velocity (TAMAX, TAMEAN), pulsatility index (PI), resistance index (RI), systolic/diastolic ratio (S/D), arterial diameter (AD), and blood flow volume (BFV), with the objective of evaluating the hemodynamic behavior of blood flow velocity parameters of the uterine artery during a short-term progesterone synchronization protocol in ewes. With respect to phases, we noted increases in the means of TAMAX and TAMEAN and decreases of EDV, PI, and RI (P < 0.05). S/D, EDV, TAMEAN, PI, RI, SD, AD, and BFV showed differences between the time of progesterone insertion and the estimated time of ovulation (which was considered the last evaluation) (P < 0.05). The PI and RI values were different when comparing the times of insertion and withdrawal of the progesterone device (PI 2.53-1.54 and RI 0.76-0.68) (P < 0.05). The PI was different with respect to side (P < 0.001), but no side effect was seen in the RI. In conclusion, the two uterine arteries behave differently under the effect of progesterone (intravaginal sponges) and the effect of estradiol during the follicular phase, and estrous phase was responsible for increasing uterine blood flow.

Assessment of peripheral markers and ultrasonographic parameters in pregnant mares receiving intramuscular or intrauterine cloprostenol.

The present study aimed to compare two methods of prostaglandin-induced abortion in mares by determining blood markers (progesterone, estradiol-17ß, alpha-fetoprotein, 13,14-dihydro-15-keto-prostaglandin-F2α (PGFM)), B-mode ultrasonographic parameters, and time until loss of fetal heartbeat. It was hypothesized that intrauterine infusion of cloprostenol results in earlier fetal compromise than intramuscular administration. Ovarian structures (number and sizes of follicles and corpora lutea area), fetal heartbeat, and fetal mobility of thirteen singleton pregnancies were assessed daily by transrectal ultrasonography until induction of pregnancy termination (60 ±â€¯2 days of gestation). Mares received 500 µg of cloprostenol intramuscularly every 12 h (IM, n = 7) or once transcervically (TC, n = 6). After initial cloprostenol administration, ultrasonographic examinations were repeated at 6-h intervals until loss of fetal heartbeat was detected. Plasma progesterone, estradiol-17ß, and alpha-fetoprotein were assessed for five days before and after pregnancy loss. In addition, plasma PGFM concentrations were assessed immediately before cloprostenol administration (0 min), and then 15, 30, and 45 min, and 1, 2, 3, 4, 6, 12 h after administration. Data were analyzed using the MIXED procedure with repeated measures in SAS. Significance was set at P < 0.05. All mares lost their pregnancies within 48 h after initial cloprostenol administration, with no difference in time to pregnancy loss. There were significant effects of time starting by 12 h post-induction of pregnancy termination but there was no time by group interaction for progesterone concentrations. Estradiol-17ß and alpha-fetoprotein concentrations were not altered upon impending abortion. Concentrations of PGFM increased significantly by 2 h after cloprostenol administration, but there were no differences between groups. No time effects or time by group interaction for fetal mobility and heartbeat was detected. Expectedly, the number and area of corpora lutea decreased significantly after cloprostenol administration with no significant differences between groups. In conclusion, intrauterine administration of cloprostenol was not different from repeated systemic administration to terminate the pregnancy. Both models for early fetal loss were equivalent for the endpoints assessed herein. The present study provides evidence that transcervical cloprostenol administration technique is repeatable in different settings and results in negligible side effects. While systemic administration results in colic-like signs and may result in severe reaction.