Comparison of antimüllerian hormone levels and antral follicle count as predictor of ovarian response to controlled ovarian stimulation in good-prognosis patients at individual fertility clinics in two multicenter trials

Objective To compare antimüllerian hormone (AMH) and antral follicle count (AFC) as predictors of ovarian response to controlled ovarian stimulation at individual fertility clinics. Design Retrospective analysis of individual study center data in two multicenter trials. Centers that provided >10 patients were included in the analysis. Setting A total of 19 (n = 519 patients) and 18 study centers (n = 686 patients) participating in a long GnRH agonist trial (MERIT) and a GnRH antagonist trial (MEGASET), respectively. Patient(s) Infertile women of good prognosis. Intervention(s) Long GnRH agonist or GnRH antagonist cycles. Main Outcome Measure(s) Correlation between AMH and AFC, and oocyte yield by each study center for each trial. Results(s) Antimüllerian hormone was more strongly correlated with oocyte yield than AFC: r = 0.56 vs. r = 0.28 in the GnRH agonist cohort, and r = 0.55 vs. r = 0.33 in the GnRH antagonist cohort. The correlation was numerically higher for AMH than for AFC at a significantly higher proportion of study centers: 17 (89%) and 15 (83%) centers in the long GnRH agonist and GnRH antagonist trial, respectively. Assessment of the relative capacity of AMH and AFC for predicting oocyte yield demonstrated that AMH dominated the model: AMH, R2 = 0.29 and 0.23; AFC: R2 = 0.07 and 0.07; AMH + AFC: R2 = 0.30 and 0.23 for long GnRH agonist and GnRH antagonist trials, respectively. Conclusions(s) Antimüllerian hormone was a stronger predictor of ovarian response to gonadotropin therapy than AFC at the study center level in both randomized trials utilizing GnRH agonist and GnRH antagonist protocols. Antral follicle count provided no added predictive value beyond AMH.</p

Antimüllerian hormone in gonadotropin releasing-hormone antagonist cycles: prediction of ovarian response and cumulative treatment outcome in good-prognosis patients

ObjectiveTo assess the relationships between serum antimüllerian hormone (AMH) and ovarian response and treatment outcomes in good-prognosis patients undergoing controlled ovarian stimulation using a gonadotropin-releasing hormone (GnRH) antagonist protocol.DesignSecondary analysis of data prospectively collected in a randomized, assessor-blind trial comparing two different gonadotropin preparations with respect to ongoing pregnancy rate.SettingTwenty-five centers in seven countries.Patient(s)749 women, aged 21 to 34 years, with primary diagnosis of infertility being unexplained infertility or mild male factor infertility and with serum follicle-stimulating hormone (FSH) level 1–12 IU/L and antral follicle count (AFC) ≥10.Intervention(s)Controlled ovarian stimulation with highly purified human menopausal gonadotropin (hphMG) or recombinant FSH in a GnRH antagonist cycle with compulsory single-blastocyst transfer and potential subsequent 1-year cryopreserved blastocyst replacement in natural cycles.Main Outcome Measure(s)Relationships between AMH at start of stimulation and ovarian response and treatment outcome.Result(s)Serum AMH concentration was strongly correlated with oocyte yield: AMH accounted for 85%, FSH for 14%, and inhibin B and AFC for <1% each of the explained variation in oocyte yield. Also, AMH showed a high accuracy for the prediction of poor (≤3 oocytes) and high response (≥15 oocytes), which was statistically significantly better than basal FSH, AFC, or inhibin B. AMH was statistically significantly positively associated with ongoing pregnancy rate in the fresh cycle as well as with the 1-year cumulative ongoing pregnancy and live-birth rates.Conclusion(s)There is a positive relationship between AMH and oocyte yield in GnRH antagonist cycles, and AMH is the best predictor for identifying patients with poor and high ovarian response. The positive association between AMH and cumulative live-birth rates after fresh and cryopreserved cycles reflects the availability of more oocytes/blastocysts, not higher quality.Clinical Trial Registration NumberNCT00884221

Follicular and endocrine dose responses according to anti-Müllerian hormone levels in IVF patients treated with a novel human recombinant FSH (FE 999049)

Objective: To study the association between serum anti-Mullerian hormone (AMH) levels and follicular development and endocrine responses induced by increasing doses (5.2-12.1 mu g/day) of a novel recombinant human FSH (rhFSH, FE 999049) in patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in a GnRH antagonist protocol. Design: Secondary analysis of a randomized controlled trial with stratified randomization according to AMH (lower stratum: 5.0-14.9 pmol/l; higher stratum: 15.0-44.9 pmol/l). Patients: Infertile women of good prognosis (n = 265). Measurements: Follicular development and endocrine parameters during controlled ovarian stimulation (COS) with rhFSH. Results: Serum FSH levels increased with increasing rhFSH doses and steady-state levels for each dose were similar in both AMH strata. In the whole study population, significant (P = 12 mm, and serum levels of oestradiol, inhibin B, inhibin A and progesterone at end of stimulation. In comparison with the higher AMH stratum, patients in the lower AMH stratum had significantly different slopes of the dose-response curves for these hormones, and no clear dose-related increase was observed for the number of follicles in these patients. Conclusions: Dose-response relationships between rhFSH and follicular development and endocrine parameters are significantly different for IVF/ICSI patients with lower and higher serum AMH levels at start of COS

Individualized versus conventional ovarian stimulation for in vitro fertilization:a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial

Objective: To compare the efficacy and safety of follitropin delta, a new human recombinant FSH with individualized dosing based on serum antimüllerian hormone (AMH) and body weight, with conventional follitropin alfa dosing for ovarian stimulation in women undergoing IVF. Design: Randomized, multicenter, assessor-blinded, noninferiority trial (ESTHER-1). Setting: Reproductive medicine clinics. Patient(s): A total of 1,329 women (aged 18–40 years). Intervention(s): Follitropin delta (AMH &lt;15 pmol/L: 12 μg/d; AMH ≥15 pmol/L: 0.10–0.19 μg/kg/d; maximum 12 μg/d), or follitropin alfa (150 IU/d for 5 days, potential subsequent dose adjustments; maximum 450 IU/d). Main Outcomes Measure(s): Ongoing pregnancy and ongoing implantation rates; noninferiority margins −8.0%. Result(s): Ongoing pregnancy (30.7% vs. 31.6%; difference −0.9% [95% confidence interval (CI) −5.9% to 4.1%]), ongoing implantation (35.2% vs. 35.8%; −0.6% [95% CI −6.1% to 4.8%]), and live birth (29.8% vs. 30.7%; −0.9% [95% CI −5.8% to 4.0%]) rates were similar for individualized follitropin delta and conventional follitropin alfa. Individualized follitropin delta resulted in more women with target response (8–14 oocytes) (43.3% vs. 38.4%), fewer poor responses (fewer than four oocytes in patients with AMH &lt;15 pmol/L) (11.8% vs. 17.9%), fewer excessive responses (≥15 or ≥20 oocytes in patients with AMH ≥15 pmol/L) (27.9% vs. 35.1% and 10.1% vs. 15.6%, respectively), and fewer measures taken to prevent ovarian hyperstimulation syndrome (2.3% vs. 4.5%), despite similar oocyte yield (10.0 ± 5.6 vs. 10.4 ± 6.5) and similar blastocyst numbers (3.3 ± 2.8 vs. 3.5 ± 3.2), and less gonadotropin use (90.0 ± 25.3 vs. 103.7 ± 33.6 μg). Conclusion(s): Optimizing ovarian response in IVF by individualized dosing according to pretreatment patient characteristics results in similar efficacy and improved safety compared with conventional ovarian stimulation

Distribution of indium in the Ánimas - Chocaya - Siete Suyos District

The Ánimas - Chocaya - Siete Suyos district in SW Bolivia hosts a Bolivian-type polymetallic vein mineralization composed mostly of cassiterite, sphalerite, pyrite, galena, stannite, lead sulfosalts, tin sulfosalts and silver sulfosalts. In addition to base (Zn, Sn, Pb) and precious (Ag) metals, important concentrations of In have been described. Systematic EPMA analyses have revealed that the highest concentrations are found in an early generation of sphalerite (up to 9.66 wt% In) and in stannite (up to 4.11 wt% In). Although In-bearing sphalerites are relatively Fe-rich (mostly between 6.0 and 18.1 mol % FeS), the atomic concentrations of these two elements do not yield any correlation. In contrast, In is positively correlated with Cu mostly along a Cu/In = 1 proportion pointing to a (In3+ + Cu+ ) ¿ 2Zn2+ coupled substitution. A relatively high activity of Cu during the crystallization of In-rich sphalerite is also supported by exsolutions of chalcopyrite and stannite.Peer ReviewedPostprint (author's final draft

Indium Mineralization in the Volcanic Dome-Hosted Ánimas-Chocaya-Siete Suyos Polymetallic Deposit, Potosí, Bolivia

A volcanic dome complex of Miocene age hosts the In-bearing Ánimas-Chocaya-Siete Suyos district in SW Bolivia. Ore mineralization occurs as banded and massive infillings in sub-vertical, NE-SW striking veins. In this article, a detailed petrographic study is combined with in situ mineral geochemistry determinations in ore from the Arturo, Chorro and Diez veins in the Siete Suyos mine, the Ánimas, Burton, Colorada, and Rosario veins in the Ánimas mine and the Nueva vein in the Chocaya mine. A three-stage paragenetic sequence is roughly determined for all of them, and includes (1) an early low-sulfidation stage that is dominated by cassiterite, pyrrhotite, arsenopyrite, and high-Fe sphalerite (FeS > 21 mol. %); (2) a second intermediate-sulfidation stage dominated by pyrite + marcasite ± intermediate product, sphalerite (FeS < 21 mol. %), stannite, and local famatinite; and, (3) a late intermediate-sulfidation stage dominated by galena and Ag-Pb-Sn sulfosalts. Electron-probe microanalyses reveal high indium enrichment in stage-2 sphalerite (up to 9.66 wt.% In) and stannite (up to 4.11 wt.% In), and a moderate enrichment in rare wurtzite (up to 1.61 wt.% In), stage-1 sphalerite (0.35 wt.% In), cassiterite (up to 0.25 wt.% In2O3), and ramdohrite (up to 0.24 wt.% In). Therefore, the main indium mineralization in the district can be associated to the second, intermediate-sulfidation stage, chiefly in those veins in which sphalerite and stannite are more abundant. Atomic concentrations of In and Cu in sphalerite yield a positive correlation at Cu/In = 1 that agrees with a (Cu+ + In3+) ↔ 2Zn2+ coupled substitution. The availability of Cu in the mineralizing fluids during the crystallization of sphalerite is, in consequence, essential for the incorporation of indium in its crystal lattice and would control the distribution of indium enrichment at different scales. The highest concentrations of indium in sphalerite, which is found in the Diez vein in the Siete Suyos mine, occur in crustiform bands of sphalerite with local "chalcopyrite disease" texture, which has not been observed in the other studied veins. In stannite, the atomic concentrations of In are negatively correlated with those of Cu and Sn at Cu + In = 2 and Sn + In = 1. Thus, atomic proportions and correlations suggest the contextualization of the main indium mineralization in the sphalerite-stannite-roquesite pseudoternary system

The Poopó Polymetallic Epithermal Deposit, Bolivia: Mineralogy, Genetic Constraints, and Distribution of Critical Elements

The tin-rich polymetallic epithermal deposit of Poopó, of plausible Late Miocene age, is part of the Bolivian Tin Belt. As an epithermal low sulfidation mineralisation, it represents a typological end-member within the "family" of Bolivian tin deposits. The emplacement of the mineralisation was controlled by the regional fault zone that constitutes the geological border between the Bolivian Altiplano and the Eastern Andes Cordillera. In addition to Sn and Ag, its economic interest resides in its potential in critical elements as In, Ga and Ge. This paper provides the first systematic characterisation of the complex mineralogy and mineral chemistry of the Poopó deposit with the twofold aim of identifying the mineral carriers of critical elements and endeavouring to ascertain plausible metallogenic processes for the formation of this deposit, by means of a multi-methodological approach. The poor development of hydrothermal alteration assemblage, the abundance of sulphosalts and the replacement of löllingite and pyrrhotite by arsenopyrite and pyrite, respectively, indicate that this deposit is ascribed to the low-sulphidation subtype of epithermal deposits, with excursions into higher states of sulphidation. Additionally, the occurrence of pyrophyllite and topaz has been interpreted as the result of discrete pulses of high-sulphidation magmatic fluids. The δ34SVCDT range in sulphides (−5.9 to −2.8 ) is compatible either with: (i) hybrid sulphur sources (i.e., magmatic and sedimentary or metasedimentary); or (ii) a sole magmatic source involving magmas that derived from partial melting of sedimentary rocks or underwent crustal assimilation. In their overall contents in critical elements (In, Ga and Ge), the key minerals in the Poopó deposit, based on their abundance in the deposit and compositions, are rhodostannite, franckeite, cassiterite, stannite and, less importantly, teallite, sphalerite and jamesonite

The Poopó polymetallic epithermal deposit, Bolivia: mineralogy, genetic constraints, and distribution of critical elements

The tin-rich polymetallic epithermal deposit of Poopó, of plausible Late Miocene age, is part of the Bolivian Tin Belt. As an epithermal low sulfidation mineralisation, it represents a typological end-member within the “family” of Bolivian tin deposits. The emplacement of the mineralisation was controlled by the regional fault zone that constitutes the geological border between the Bolivian Altiplano and the Eastern Andes Cordillera. In addition to Sn and Ag, its economic interest resides in its potential in critical elements as In, Ga and Ge. This paper provides the first systematic characterisation of the complex mineralogy and mineral chemistry of the Poopó deposit with the twofold aim of identifying the mineral carriers of critical elements and endeavouring to ascertain plausible metallogenic processes for the formation of this deposit, by means of a multi-methodological approach. The poor development of hydrothermal alteration assemblage, the abundance of sulphosalts and the replacement of löllingite and pyrrhotite by arsenopyrite and pyrite, respectively, indicate that this deposit is ascribed to the low-sulphidation subtype of epithermal deposits, with excursions into higher states of sulphidation. Additionally, the occurrence of pyrophyllite and topaz has been interpreted as the result of discrete pulses of high-sulphidation magmatic fluids. The d34SVCDT range in sulphides (-5.9 to -2.8‰) is compatible either with: (i) hybrid sulphur sources (i.e., magmatic and sedimentary or metasedimentary); or (ii) a sole magmatic source involving magmas that derived from partial melting of sedimentary rocks or underwent crustal assimilation. In their overall contents in critical elements (In, Ga and Ge), the key minerals in the Poopó deposit, based on their abundance in the deposit and compositions, are rhodostannite, franckeite, cassiterite, stannite and, less importantly, teallite, sphalerite and jamesonite.Peer ReviewedPostprint (published version

Spatial and Temporal Controls on the Distribution of Indium in Xenothermal Vein-Deposits: The Huari Huari District, Potosí, Bolivia

The Huari Huari deposit, Potosí Department in SW Bolivia, hosts polymetallic stratiform and vein mineralization of Miocene age with significant concentrations of the critical metal indium (In). Vein mineralization records document early crystallization of quartz and cassiterite followed by prominent associations of sulfides and sulfosalts. The earliest sulfide was arsenopyrite, followed by pyrrhotite, and progressively giving way to pyrite as the main iron sulfide, whereas Cu-Ag-Pb sulfosalts constitute late hypogene associations. Sphalerite is the chief ore mineral, and its crystallization is extended during most of the mineralization lifespan as evidenced by its initial cocrystallization with pyrrhotine, then with pyrite, and finally with Ag-Pb sulfosalts. The composition of sphalerite varies from early to late generations with a continuous decrease in FeS that attests to a decrease in temperature, which is constrained to vary from ~450 to <200 °C, and/or an increase in f(S2), both congruent with the described paragenetic sequence. Indium concentrated mostly in the structure of Fe-rich sphalerite (up to 3.49 wt. %) and stannite (up to 2.64 wt. %) as limited solid solutions with roquesite in the (Zn,Fe)S-Cu2FeSnS4-CuInS2 pseudoternary system. In sphalerite, In shows a strong positive correlation with Cu at Cu/In = 1, suggesting its incorporation via a (Cu+ + In3+) ↔ 2Zn2+ coupled substitution, and it does not correlate with Fe. In stannite, In shows a moderate, negative correlation with Cu and Sn, and an In3+ ↔ (Cu+ + ½ Sn4+) coupled substitution is suggested. Coexisting sphalerite and stannite yielded the highest In concentrations and crystallized at temperatures between 350 and 250 °C. Copper activity probably played a major role in the accumulation of In in the structure of sphalerite since In-bearing sphalerite coexisted with the deposition of stannite, shows high concentrations of Cu (up to 0.13 atoms per formula unit (a.p.f.u.)) in its structure, and hosts exsolutions of stannite and chalcopyrite. Distribution on the district scale of In suggests an input of hydrothermal fluids richer in Cu in the central position of the mineralizing system, represented by the Antón Bravo vein