RESEARCH QUESTION: How does the efficacy and safety of individualized follitropin delta dosing compare with conventional dosing for ovarian stimulation in potential high responders? DESIGN: Retrospective analysis of 153 potential high responders identified on the basis of baseline serum anti-Müllerian hormone (AMH) levels above 35 pmol/l, who were originally randomized to an individualized fixed dose of follitropin delta based on AMH and body weight (n = 78) or to a daily starting dose of 150 IU follitropin alfa (n = 75). RESULTS: At the end of stimulation, patients treated with individualized follitropin delta or conventional follitropin alfa had 12.1 ± 7.0 and 18.3 ± 7.0 (P < 0.001) follicles measuring 12 mm or wider, and 27.3% and 62.7% had serum progesterone levels higher than 3.18 nmol/l (P < 0.001), respectively. Overall number of oocytes in these two respective arms was 9.3 ± 6.7 and 17.9 ± 8.7 (P < 0.001), and the ongoing pregnancy rate per started cycle after fresh blastocyst transfer was 28.2% and 24.0%. The risk of ovarian hyperstimulation syndrome (OHSS) for all cases was three times higher in the conventional follitropin alfa arm at 16.0% versus 5.1% with individualized follitropin delta treatment (P = 0.025) and 26.7% versus 7.7% (P = 0.001) for early moderate or severe OHSS, preventive interventions for early OHSS, or both. CONCLUSIONS: Treatment with individualized follitropin delta provides an improved efficacy-safety balance in women with high ovarian reserve, as it normalizes the ovarian response and decreases the risk of OHSS without compromising the chance of pregnancy.

• MeSH
• antimülleriánský hormon krev   MeSH
• dospělí MeSH
• fertilizace in vitro metody   MeSH
• folikuly stimulující hormon lidský aplikace a dávkování   MeSH
• indukce ovulace škodlivé účinky   MeSH
• lidé MeSH
• ovariální hyperstimulační syndrom krev   etiologie   MeSH
• porodnost MeSH
• progesteron krev   MeSH
• rekombinantní proteiny aplikace a dávkování   MeSH
• retrospektivní studie MeSH
• těhotenství MeSH
• tělesná hmotnost fyziologie   MeSH
• úhrn těhotenství na počet žen v reprodukčním věku MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

RESEARCH QUESTION: Is individualization of dosing with follitropin delta in sequential ovarian stimulation cycles an effective preventive strategy for ovarian hyperstimulation syndrome risk? If so, for which patients does an individualized strategy provide the greatest OHSS risk reduction and/or the need for additional preventive interventions? DESIGN: A secondary analysis of three ovarian stimulation cycles in IVF/intracytoplasmic sperm injection patients included in one randomized, assessor-blinded trial comparing two recombinant FSH preparations (ESTHER-1, NCT01956110), and a second trial in women undergoing up to two additional cycles (ESTHER-2, NCT01956123). Of 1326 women (aged 18-40 years) randomized and treated with follitropin delta or alfa in cycle 1, 513 continued to cycle 2 and 188 to cycle 3. Follitropin delta and alfa doses were maintained/adjusted according to ovarian response in the previous cycle. RESULTS: Individualized dosing with follitropin delta significantly reduced moderate/severe OHSS and/or preventive interventions (P=0.018) versus conventional dosing with follitropin alfa in patients undergoing up to three ovarian stimulation cycles. The greatest benefit was observed in patients in the highest anti-Müllerian hormone (AMH) quartile (P=0.012). On evaluating separately, individualized dosing with follitropin delta significantly lowered the incidences of moderate/severe OHSS (P=0.036) and preventive interventions (P=0.044) versus follitropin alfa. CONCLUSION: An individualized follitropin delta dosing regimen decreased the risk of moderate/severe OHSS as well as the incidence of preventive interventions versus a conventional follitropin alfa regimen. An analysis per AMH quartile indicated that these statistically significant differences are driven mainly by patients with the highest pretreatment AMH levels.

• MeSH
• dospělí MeSH
• fertilizace in vitro MeSH
• folikuly stimulující hormon lidský aplikace a dávkování   terapeutické užití   MeSH
• indukce ovulace * škodlivé účinky   MeSH
• interpretace statistických dat MeSH
• intracytoplazmatické injekce spermie MeSH
• kryoprezervace MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• ovariální hyperstimulační syndrom prevence a kontrola   MeSH
• ovarium účinky léků   MeSH
• rekombinantní proteiny aplikace a dávkování   terapeutické užití   MeSH
• riziko MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

• MeSH
• choriogonadotropin aplikace a dávkování   MeSH
• fertilizace in vitro * metody   MeSH
• folikuly stimulující hormon lidský aplikace a dávkování   MeSH
• hormon uvolňující gonadotropiny analogy a deriváty   aplikace a dávkování   MeSH
• indukce ovulace * metody   MeSH
• lidé MeSH
• luteální fáze účinky léků   MeSH
• medroxyprogesteron aplikace a dávkování   MeSH
• progestiny aplikace a dávkování   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH

OBJECTIVE: To evaluate the dose-response relationship of a novel recombinant human FSH (rhFSH; FE 999049) with respect to ovarian response in patients undergoing IVF/intracytoplasmic sperm injection treatment; and prospectively study the influence of initial antimüllerian hormone (AMH) concentrations. DESIGN: Randomized, controlled, assessor-blinded, AMH-stratified (low: 5.0-14.9 pmol/L [0.7-<2.1 ng/mL]; high: 15.0-44.9 pmol/L [2.1-6.3 ng/mL]) trial. SETTING: Seven infertility centers in four countries. PATIENT(S): Two hundred sixty-five women aged ≤37 years. INTERVENTION(S): Controlled ovarian stimulation with either 5.2, 6.9, 8.6, 10.3, or 12.1 μg of rhFSH, or 11 μg (150 IU) of follitropin alfa in a GnRH antagonist cycle. MAIN OUTCOME MEASURE(S): Number of oocytes retrieved. RESULT(S): The number of oocytes retrieved increased in an rhFSH dose-dependent manner, from 5.2 ± 3.3 oocytes with 5.2 μg/d to 12.2 ± 5.9 with 12.1 μg/d. The slopes of the rhFSH dose-response curves differed significantly between the two AMH strata, demonstrating that a 10% increase in dose resulted in 0.5 (95% confidence interval 0.2-0.7) and 1.0 (95% confidence interval 0.7-1.3) more oocytes in the low and high AMH stratum, respectively. Fertilization rate and blastocyst/oocyte ratio decreased significantly with increasing rhFSH doses in both AMH strata. No linear relationship was observed between rhFSH dose and number of blastocysts overall or by AMH strata. Five cases of ovarian hyperstimulation syndrome were reported for the three highest rhFSH doses and in the high AMH stratum. CONCLUSION(S): Increasing rhFSH doses results in a linear increase in number of oocytes retrieved in an AMH-dependent manner. The availability of blastocysts is less influenced by the rhFSH dose and AMH level. CLINICAL TRIAL REGISTRATION NUMBER: NCT01426386.

• MeSH
• antimülleriánský hormon aplikace a dávkování   MeSH
• dospělí MeSH
• fertilizace in vitro metody   MeSH
• folikuly stimulující hormon lidský aplikace a dávkování   MeSH
• indukce ovulace metody   MeSH
• intracytoplazmatické injekce spermie metody   MeSH
• lidé MeSH
• odběr oocytu * MeSH
• rekombinantní proteiny aplikace a dávkování   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

To evaluate whether a short follicular phase of ovarian stimulation compromises the chance of pregnancy, subjects from a double-blind, randomized trial treated with a single dose of corifollitropin alfa (n=756) or daily recombinant FSH (n=750) were categorized as early responders if three follicles ≥17 mm were reached and human chorionic gonadotrophin (HCG) was administered prior to or on stimulation day 8, and as normal responders if three follicles ≥17 mm were reached and HCG was administered after stimulation day 8. In the corifollitropin alfa and recombinant FSH groups, 23.2% and 29.1%, respectively, were early responders (P=0.01). Regardless of the treatment group, the initial ovarian response was higher in early responders, but with two extra days of stimulation, the number and size of follicles on the day of HCG in the normal responders was similar to those of the early responders. The number of oocytes was similar in both response groups following corifollitropin alfa treatment (13.6 versus 14.5) and recombinant FSH treatment (12.8, both groups). The ongoing pregnancy rates were comparable for early and normal responders regardless of the treatment group, supporting successful outcome following a stimulation period of only 1 week.

• MeSH
• časové faktory MeSH
• choriogonadotropin aplikace a dávkování   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• folikulární fáze fyziologie   MeSH
• folikuly stimulující hormon lidský aplikace a dávkování   MeSH
• folikuly stimulující hormon aplikace a dávkování   MeSH
• indukce ovulace metody   MeSH
• lidé MeSH
• rekombinantní proteiny aplikace a dávkování   MeSH
• retrospektivní studie MeSH
• těhotenství MeSH
• úhrn těhotenství na počet žen v reprodukčním věku MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

PURPOSE: To prevent multiple pregnancies the goal of ovulation induction by gonadotropins is to achieve only mono-follicular development. The most important issue is therefore to determine the starting dose. The aim of this study is to compare three different starting doses of follitropin beta to assess the lowest effective dose. METHODS: We evaluated 92 cycles with ovarian stimulation for patients with unexplained infertility, anovulatory disorder or mild male factor. We prospectively divided patients into 50, 75 and 100 IU groups based on patients' response to clomiphene citrate treatment. RESULTS: We performed 87 intrauterine inseminations (95 % of cycles with ovulation induction). Five cycles were cancelled. We achieved 15 pregnancies; total pregnancy rate was 18 %. Pregnancy rate was 22, 10 and 28 % in 50, 75 and 100 IU follitropin beta groups. The average number of follicles was 2.0 ± 0.8, 2.2 ± 1.1 and 2.5 ± 1.8 (ns), total dose of gonadotropins (IU) 483 ± 192, 600 ± 151 and 830 ± 268 (p < 0.001), respectively. We observed one case of twins in 75 and 100 IU treatment group, as well (25 % risk). CONCLUSIONS: This study suggests that based on the dose which was chosen according to clomiphene citrate response, all treatment regimes were effective for ovulation induction. 50 IU of follitropin beta daily is the appropriate starting dose to support ovulation for clomiphene citrate-sensitive women. The disadvantage may be an increased risk of cycle cancellation due to low ovarian response. Daily doses 75 or 100 IU of rFSH increase total consumption of gonadotropins.

• MeSH
• dospělí MeSH
• endometrium účinky léků   MeSH
• folikuly stimulující hormon lidský aplikace a dávkování   MeSH
• indukce ovulace metody   MeSH
• lidé MeSH
• ovariální folikul účinky léků   MeSH
• ovariální hyperstimulační syndrom epidemiologie   MeSH
• prospektivní studie MeSH
• rekombinantní proteiny aplikace a dávkování   MeSH
• těhotenství mnohočetné statistika a číselné údaje   MeSH
• těhotenství MeSH
• úhrn těhotenství na počet žen v reprodukčním věku * MeSH
• umělá inseminace MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• srovnávací studie MeSH