Cíl: Zaměřili jsme se na srovnání vysoce purifikovaný lidský menopauzální gonadotropin (hp-hMG) a rekombinantní folikuly stimulující hormon (rFSH) v krátkých antagonistických cyklech in vitro fertilizace (IVF) u pacientek se špatnou ovariální rezervou (POR). Pro tuto skupinu pacientek existuje omezený výzkum tohoto srovnání v krátkých cyklech antagonistů. Materiály a metody: Tato retrospektivní kohortová studie zahrnovala 165 pacientek s POR ve věku 18–45 let, kteří podstoupili IVF v letech 2018–2022. Pacienti byli rozděleni do dvou skupin na základě protokolu s antagonistou GnRH: hp-hMG (skupina 1 = 72) a rFSH (skupina 2 = 93). Porovnávali jsme výsledky těhotenství, počet odebraných oocytů, odebrané zralé oocyty, průměrný počet oplodněných oocytů, transferovaná embrya nejvyšší kvality a hladiny sérového estradiolu (E2) a progesteronu (P) v den podání hCG. Výsledky: Nebyly nalezeny žádné signifikantní rozdíly v hladinách E2 a P v den spouštění hCG, tloušťce endometria v den přenosu, délce stimulace, celkovém počtu oocytů a počtu zralých oocytů (p > 0,05). Celková dávka gonadotropinu byla významně vyšší ve skupině s rFSH (p < 0,001). Počet transferovaných embryí špičkové kvality a klinické těhotenství a porodnost se mezi skupinami významně nelišily (p = 0,320; p = 0,310; p = 0,652 a p = 0,662). Závěr: Ani hp-hMG ani rFSH neprokázaly převahu u pacientek s POR, což ukazuje na podobnou účinnost v této populaci.
Objective: We aimed to compare highly purified human menopausal gonadotropin (hp-hMG) and recombinant follicle stimulating hormone (rFSH) in short antagonist in vitro fertilization (IVF) cycles of patients with poor ovarian reserve (POR). Limited research exists on this comparison in short antagonist cycles for this patient group. Materials and methods: This retrospective cohort study involved 165 POR patients aged 18–45 years who underwent IVF between 2018 and 2022. Patients were divided into two groups based on their GnRH antagonist protocol: hp-hMG (group 1 = 72) and rFSH (group 2 = 93). We compared pregnancy outcomes, number of oocytes collected, mature oocytes retrieved, mean fertilized oocytes, top quality embryos transferred, and serum estradiol (E2) and progesterone (P) levels on human chorionic gonadotropin (hCG) administration day. Results: No significant differences were found in E2 and P levels on hCG trigger day, endometrial thickness on transfer day, stimulation duration, total oocyte number, and mature oocyte number (P > 0.05). The total gonadotropin dose was significantly higher in the rFSH group (P < 0.001). The number of top-quality embryos transferred and clinical pregnancy and live birth rates did not differ significantly between groups (P = 0.320; P = 0.310; P = 0.652; and P = 0.662, resp.). Conclusion: Neither hp-hMG nor rFSH showed superiority in patients with POR, indicating similar effectiveness in this population.
- MeSH
- fertilizace in vitro metody MeSH
- folikuly stimulující hormon * aplikace a dávkování terapeutické užití MeSH
- indukce ovulace metody MeSH
- lidé MeSH
- menotropiny * aplikace a dávkování terapeutické užití MeSH
- ovariální rezerva * účinky léků MeSH
- retrospektivní studie MeSH
- těhotenství účinky léků MeSH
- Check Tag
- lidé MeSH
- těhotenství účinky léků MeSH
STUDY QUESTION: Does addition of choriogonadotropin beta (recombinant CG beta) to follitropin delta increase the number of good-quality blastocysts following ovarian stimulation in a long GnRH agonist protocol? SUMMARY ANSWER: At the doses investigated, the addition of CG beta reduced the number of intermediate follicles and related down-stream parameters including the number of oocytes and blastocysts. WHAT IS KNOWN ALREADY: CG beta is a novel recombinant hCG (rhCG) molecule expressed by a human cell line (PER.C6®) and has a different glycosylation profile compared to urinary hCG or rhCG derived from a Chinese Hamster Ovary (CHO) cell line. In the first-in-human trial, the CG beta pharmacokinetics were similar between men and women. In women, the AUC and the peak serum concentration (Cmax) increased approximately dose proportionally following single and multiple daily doses. In men, a single dose of CG beta provided higher exposure with a longer half-life and proportionately higher testosterone production than CHO cell-derived rhCG. STUDY DESIGN, SIZE, DURATION: This placebo-controlled, double-blind, randomized trial (RAINBOW) was conducted in five European countries to explore the efficacy and safety of CG beta as add-on treatment to follitropin delta in women undergoing ovarian stimulation in a long GnRH agonist protocol. Randomization was stratified by centre and age (30-37 and 38-42 years). The primary endpoint was the number of good-quality blastocysts (Grade 3 BB or higher). Subjects were randomized to receive either placebo or 1, 2, 4, 8 or 12 μg CG beta added to the daily individualized follitropin delta dose during ovarian stimulation. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 620 women (30-42 years) with anti-Müllerian hormone (AMH) levels between 5 and 35 pmol/l were randomized in equal proportions to the six treatment groups and 619 subjects started treatment. All 619 subjects were treated with an individualized dose of follitropin delta determined based on AMH (Elecsys AMH Plus Immunoassay) and body weight. Triggering with rhCG was performed when 3 follicles were ≥17 mm but no more than 25 follicles ≥12 mm were reached. MAIN RESULTS AND THE ROLE OF CHANCE: The demographic characteristics were comparable between the six treatment groups and the overall mean age, body weight and AMH were 35.6 ± 3.3 years, 65.3 ± 10.7 kg and 15.3 ± 7.0 pmol/l, respectively. The incidence of cycle cancellation (range 0-2.9%), total follitropin delta dose (mean 112 μg) and duration of stimulation (mean 10 days) were similar across the groups. At stimulation Day 6, the number and size of follicles was similar between the treatment groups, whereas at the end-of-stimulation dose-related decrease of the intermediate follicles between 12 and 17 mm was observed in comparison to the placebo group. In contrast, the number of follicles ≥17 mm was similar between the CG beta dose groups and the placebo group. A reduced number of intermediate follicles (12 to 17 mm) and fewer oocytes (mean range 9.7 to 11.2) were observed for all doses of CG beta compared to the follitropin delta only group (mean 12.5). The mean number of good-quality blastocysts was 3.3 in the follitropin delta group and ranged between 2.1 and 3.0 across the CG beta groups. The incidence of transfer cancellation was higher in the 4, 8 and 12 μg group, mostly as no blastocyst was available for transfer. In the group receiving only follitropin delta, the ongoing pregnancy rate (10-11 weeks after transfer) was 43% per started cycle versus 28-39% in CG beta groups and 49% per transfer versus 38-50% in the CG beta groups. There was no apparent effect of CG beta on the incidence of adverse events, which was 48.1% in the placebo group and 39.6-52.3% in the CG beta dose groups. In line with the number of collected oocytes, the overall ovarian hyperstimulation syndrome incidence remained lower following follitropin delta with CG beta (2.0-10.3%) compared with follitropin delta only treatment (11.5%). Regardless of the dose, CG beta was safe and well-tolerated with low risk of immunogenicity. LIMITATIONS, REASONS FOR CAUTION: The effect of the unique glycosylation of CG beta and its associated potency implications in women were not known prior to this trial. Further studies will be needed to evaluate optimal doses of CG beta for this and/or different indications. WIDER IMPLICATIONS OF THE FINDINGS: The high ongoing pregnancy rate in the follitropin delta group supports the use of individualized follitropin delta dosing in a long GnRH agonist protocol. The addition of CG beta reduced the presence of intermediate follicles with the investigated doses and negatively affected all down-stream parameters. Further clinical research will be needed to assess the optimal dose of CG beta in the optimal ratio to follitropin delta to develop this novel combination product containing both FSH and LH activity for ovarian stimulation. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by Ferring Pharmaceuticals, Copenhagen, Denmark. B.M. and P.L. are employees of Ferring Pharmaceuticals. M.F.S., H.V., C.Y.A., M.F., C.B., A.P. and Y.K. have received institutional clinical trial fees from Ferring Pharmaceuticals. C.B. has received payments for lectures from Organon, Ferring Pharmaceuticals, Merck A/S and Abbott. M.F.S. has received payment for lectures from Ferring Pharmaceuticals. Y.K. has received payment for lectures from Merck and travel support from Gedeon Richter. H.V. has received consulting fees from Oxo and Obseva and travel support from Gedeon Richter, Ferring Pharmaceuticals and Merck. C.Y.A. has received payment for lectures from IBSA, Switzerland. M.F and C.Y.A. were reimbursed as members of the Data Monitoring Board in this trial. M.F. has an issued patent about unitary combination of FSH and hCG (EP1633389). TRIAL REGISTRATION NUMBER: 2017-003810-13 (EudraCT Number). TRIAL REGISTRATION DATE: 21 May 2018. DATE OF FIRST PATIENT’S ENROLMENT: 13 June 2018.
- MeSH
- antimülleriánský hormon MeSH
- CHO buňky MeSH
- choriogonadotropin MeSH
- Cricetulus MeSH
- fertilizace in vitro metody MeSH
- folikuly stimulující hormon lidský * MeSH
- hormon uvolňující gonadotropiny MeSH
- indukce ovulace * metody MeSH
- křečci praví MeSH
- léčivé přípravky MeSH
- lidé MeSH
- lidský choriogonadotropin, beta podjednotka MeSH
- randomizované kontrolované studie jako téma MeSH
- rekombinantní proteiny MeSH
- těhotenství MeSH
- tělesná hmotnost MeSH
- úhrn těhotenství na počet žen v reprodukčním věku MeSH
- zvířata MeSH
- Check Tag
- křečci praví MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- protokol klinické studie MeSH
This cross-sectional clinical study was designed to explore the impact of tryptophan-kynurenine and tryptophan-serotonin (5 HT) pathways on reproductive performance during in vitro fertilization (IVF). Paired serum and follicular fluid (FF) samples were obtained from 64 consecutive IVF patients. The analysis was done by using LC-MS/MS. Ovarian hyperstimulation resulted in decreased serum tryptophan (p<0.004), 5-HT (p<0.049) and kynurenine (p<0.001). FF levels of tryptophan (R=0.245, p<0.051), kynurenine (R=0.556, p<0.001) and 5-HT (R=0.523, p<0.001) were positively related to their respective serum levels. Clinical pregnancy was associated with higher serum 5-HT (p<0.045) and FF 5-HT (p<0.020) and lower kynurenine to 5-HT ratio (p<0.024). Chemical pregnancy was also positively related to FF 5-HT (R=0.362, p<0.024). Moreover, there was a direct relationship of the number of mature oocytes to the FF 5-HT (R=0.363, p<0.020) but it was inversely related to FF tryptophan to 5-HT and FF kynurenine to 5-HT ratios (R=-0.389, p<0.016 and R=-0.337, p<0.036, respectively). Multivariate logistic regression revealed that the number of mature oocytes was significantly influenced by FF 5-HT (?=0.473, p<0.001). In IVF patients ovarian hyperstimulation results in a reduction of the availability of tryptophan to catabolic pathways to kynurenine and 5-HT. Outcome measures improved significantly when 5-HT predominated over kynurenine.
- MeSH
- dospělí MeSH
- endometrióza metabolismus patologie MeSH
- fertilizace in vitro metody MeSH
- indukce ovulace metody MeSH
- kynurenin metabolismus MeSH
- lidé MeSH
- průřezové studie MeSH
- serotonin metabolismus MeSH
- těhotenství MeSH
- tryptofan metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- asistovaná reprodukce * MeSH
- endometrium účinky léků MeSH
- folikuly stimulující hormon terapeutické užití MeSH
- gonadotropiny terapeutické užití MeSH
- hormon uvolňující gonadotropiny agonisté antagonisté a inhibitory terapeutické užití MeSH
- indukce ovulace * metody MeSH
- lidé MeSH
- luteální fáze účinky léků MeSH
- luteinizační hormon terapeutické užití MeSH
- modulátory estrogenních receptorů terapeutické užití MeSH
- ovariální hyperstimulační syndrom * etiologie patofyziologie terapie MeSH
- progestiny terapeutické užití MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- přehledy MeSH
- Klíčová slova
- Clostilbegyt, Femara, Dracenax, Lerana,
- MeSH
- anovulace * etiologie farmakoterapie MeSH
- gonadotropiny aplikace a dávkování ekonomika farmakologie MeSH
- indukce ovulace ekonomika metody MeSH
- inhibitory aromatasy aplikace a dávkování farmakokinetika farmakologie MeSH
- klomifen aplikace a dávkování farmakologie MeSH
- letrozol aplikace a dávkování farmakokinetika farmakologie MeSH
- lidé MeSH
- náklady na léky MeSH
- přehodnocení terapeutických indikací léčivého přípravku MeSH
- ženská infertilita etiologie farmakoterapie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- asistovaná reprodukce * MeSH
- časové faktory MeSH
- choriogonadotropin aplikace a dávkování MeSH
- diagnostické techniky porodnicko-gynekologické MeSH
- endosonografie metody MeSH
- hormon uvolňující gonadotropiny agonisté aplikace a dávkování MeSH
- indukce ovulace metody MeSH
- lidé MeSH
- luteinizační hormon účinky léků MeSH
- oocyty růst a vývoj účinky léků MeSH
- ovulace účinky léků MeSH
- vagina MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví 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
- MeSH
- indukce ovulace metody MeSH
- IVM techniky metody MeSH
- kryoprezervace metody MeSH
- léčba šetřící orgány metody MeSH
- lidé MeSH
- nádory epidemiologie farmakoterapie MeSH
- odběr oocytu metody MeSH
- protinádorové látky škodlivé účinky terapeutické užití toxicita MeSH
- uchovávání tkání metody MeSH
- zachování plodnosti * metody MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Klíčová slova
- stimulační protokoly,
- MeSH
- antimülleriánský hormon analýza fyziologie MeSH
- fertilizace in vitro * MeSH
- gonadotropiny analýza terapeutické užití MeSH
- hormon uvolňující gonadotropiny agonisté antagonisté a inhibitory terapeutické užití MeSH
- indukce ovulace * metody MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH