Historicky spíše ignorovaná mužská neplodnost zapříčiňuje samostatně nebo v kombinaci neplodnost páru přibližně v 60 % případů. Nemožnost páru zplodit potomka vede k psychosociálnímu stresu. Úlohou systematické diagnostiky a terapie neplodnosti muže je rozpoznání příčiny, snaha o zlepšení tvorby spermií a zvýšení šance na úspěšné početí.

Historically rather ignored male infertility is alone or in combination the cause of approximately 60% infertile couples. Inability of couple to conceive leads to psychosocial stress. Role of systematic diagnostics and treatment of male infertility is to understand the cause, improve spermatogenesis and increase chances of successful fertilization.

• MeSH
• analýza spermatu metody   MeSH
• antioxidancia terapeutické užití   MeSH
• choriogonadotropin aplikace a dávkování   terapeutické užití   MeSH
• diagnostické techniky endokrinologické MeSH
• genetické testování MeSH
• inhibitory aromatasy terapeutické užití   MeSH
• mužská infertilita * diagnóza   etiologie   farmakoterapie   MeSH
• selektivní modulátory estrogenních receptorů aplikace a dávkování   terapeutické užití   MeSH
• Check Tag
• mužské pohlaví MeSH

STUDY QUESTION: Which actively translated maternal transcripts are differentially regulated between clinically relevant in vitro and in vivo maturation (IVM) conditions in mouse oocytes and zygotes? SUMMARY ANSWER: Our findings uncovered significant differences in the global transcriptome as well as alterations in the translation of specific transcripts encoding components of energy production, cell cycle regulation, and protein synthesis in oocytes and RNA metabolism in zygotes. WHAT IS KNOWN ALREADY: Properly regulated translation of stored maternal transcripts is a crucial factor for successful development of oocytes and early embryos, particularly due to the transcriptionally silent phase of meiosis. STUDY DESIGN, SIZE, DURATION: This is a basic science study utilizing an ICR mouse model, best suited for studying in vivo maturation. In the treatment group, fully grown germinal vesicle oocytes from stimulated ovaries were in vitro matured to the metaphase II (MII) stage either as denuded without gonadotropins (IVM DO), or as cumulus-oocyte complexes (IVM COC) in the presence of 0.075 IU/ml recombinant FSH (rFSH) and 0.075 IU/ml recombinant hCG (rhCG). To account for changes in developmental competence, IVM COC from non-stimulated ovaries (IVM COC-) were included. In vivo matured MII oocytes (IVO) from stimulated ovaries were used as a control after ovulation triggering with rhCG. To simulate standard IVM conditions, we supplemented media with amino acids, vitamins, and bovine serum albumin. Accordingly, in vitro pronuclear zygotes (IMZ) were generated by IVF from IVM DO, and were compared to in vivo pronuclear zygotes (IVZ). All experiments were performed in quadruplicates with samples collected for both polyribosome fractionation and total transcriptome analysis. Samples were collected over three consecutive months. PARTICIPANTS/MATERIALS, SETTING, METHODS: All ICR mice were bred under legal permission for animal experimentation (no. MZE-24154/2021-18134) obtained from the Ministry of Agriculture of the Czech Republic. Actively translated (polyribosome occupied) maternal transcripts were detected in in vitro and in vivo matured mouse oocytes and zygotes by density gradient ultracentrifugation, followed by RNA isolation and high-throughput RNA sequencing. Bioinformatic analysis was performed and subsequent data validation was done by western blotting, radioactive isotope, and mitotracker dye labelling. MAIN RESULTS AND THE ROLE OF CHANCE: Gene expression analysis of acquired polysome-derived high-throughput RNA sequencing data revealed significant changes (RPKM ≥ 0.2; P ≤ 0.005) in translation between in vitro and in vivo matured oocytes and respectively produced pronuclear zygotes. Surprisingly, the comparison between IVM DO and IVM COC RNA-seq data of both fractionated and total transcriptome showed very few transcripts with more than a 2-fold difference. Data validation by radioactive isotope labelling revealed a decrease in global translation bof20% in IVM DO and COC samples in comparison to IVO samples. Moreover, IVM conditions compromised oocyte energy metabolism, which was demonstrated by both changes in polysome recruitment of each of 13 mt-protein-coding transcripts as well as by validation using mitotracker red staining. LARGE SCALE DATA: The data discussed in this publication have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO Series accession number GSE241633 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE241633). LIMITATIONS, REASONS FOR CAUTION: It is extremely complicated to achieve in vivo consistency in animal model systems such as porcine or bovine. To achieve a high reproducibility of in vivo stimulations, the ICR mouse model was selected. However, careful interpretation of our findings with regard to assisted reproductive techniques has to be made by taking into consideration intra-species differences between the mouse model and humans. Also, the sole effect of the cumulus cells' contribution could not be adequately addressed by comparing IVM COC and IVM DO, because the IVM DO were matured without gonadotropin supplementation. WIDER IMPLICATIONS OF THE FINDINGS: Our findings confirmed the inferiority of standard IVM technology compared with the in vivo approach. It also pointed at compromised biological processes employed in the critical translational regulation of in vitro matured MII oocytes and pronuclear zygotes. By highlighting the importance of proper translational regulation during in vitro oocyte maturation, this study should prompt further clinical investigations in the context of translation. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Czech Grant Agency (22-27301S), Charles University Grant Agency (372621), Ministry of Education, Youth and Sports (EXCELLENCE CZ.02.1.01/0.0/0.0/15_003/0000460 OP RDE), and Institutional Research Concept RVO67985904. No competing interest is declared.

• MeSH
• choriogonadotropin farmakologie   MeSH
• embryonální vývoj * fyziologie   MeSH
• IVM techniky * MeSH
• kumulární buňky * metabolismus   MeSH
• myši inbrední ICR * MeSH
• myši MeSH
• oocyty * metabolismus   MeSH
• proteosyntéza MeSH
• transkriptom MeSH
• vývojová regulace genové exprese MeSH
• zvířata MeSH
• zygota metabolismus   MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Tubární potrat představuje vypuzení plodu z vejcovodu do dutiny břišní. Může být kompletní nebo nekompletní s rezidui přetrvávajícími ve vejcovodu. Jedná se o formu mimoděložního těhotenství, jejíž incidenci nelze přesně stanovit. Rozpoznání případů tubárního abortu je zásadní v péči o pacientku, protože může vést ke konzervativnějšímu přístupu. Diagnóza by měla být stanovena kombinací ultrazvukového vyšetření, hladiny b-hCG a peroperačního nálezu. Článek popisuje případ 30leté pacientky přijaté pro suspektní mimoděložní graviditu, kdy ultrazvukové vyšetření prokázalo masu připomínající tubární graviditu vedle dělohy a hladiny b-hCG byly 111,8 U/l. Peroperačně byl zjištěn tubární abort v Douglasově prostoru umožňující zachování obou vejcovodů. Histopatologický rozbor potvrdil klinickou diagnózu. Konzervativní přístup může mít dostatečný efekt v případě tubárního abortu, což umožňuje zachování fertility a tubárních funkcí.

Tubal abortion is characterized by the extrusion of the foetus into the abdominal (peritoneal) cavity. It can either be a complete extrusion or incomplete with residual tissue remaining in the fallopian tube. It is a type of ectopic pregnancy that is difficult to determine the exact incidence of tubal pregnancies. Identifying cases of tubal abortions is crucial for individualized care since it can lead to a more conservative treatment approach. The diagnosis should be based on ultrasound imaging, b-hCG levels and visual conformation during exploratory surgery, either open or laparoscopic. The article describes the case of a 30-year old patient who presented with lower abdominal pain and was admitted for a suspected ectopic pregnancy. Ultrasound imaging showed a mass resembling a tubal pregnancy next to the uterus with b-hCG levels of 111.8 U/L. During laparoscopic surgery, a tubal abortion was detected in the pouch of Douglas (Rectouterine pouch). This finding led us to preserve both fallopian tubes. Histopathology confirmed our clinical findings. A conservative approach can be sufficient in case of tubal abortions, which can lead to preserved fertility and tubal functions.

• MeSH
• dospělí MeSH
• Douglasův prostor diagnostické zobrazování   patologie   MeSH
• gynekologické chirurgické výkony metody   MeSH
• laparoskopie MeSH
• lidé MeSH
• lidský choriogonadotropin, beta podjednotka analýza   MeSH
• mimoděložní těhotenství * chirurgie   diagnostické zobrazování   patologie   MeSH
• salpingektomie MeSH
• samovolný potrat * chirurgie   diagnostické zobrazování   patologie   MeSH
• těhotenství MeSH
• ultrasonografie MeSH
• uterus diagnostické zobrazování   patologie   MeSH
• vejcovody chirurgie   diagnostické zobrazování   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

• MeSH
• choriogonadotropin * krev   MeSH
• dospělí MeSH
• kvantitativní polymerázová řetězová reakce metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikrosatelitní repetice MeSH
• mladý dospělý MeSH
• mola hydatidosa klasifikace   krev   patofyziologie   MeSH
• nomogramy * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• klinická studie MeSH

Immunochemical reactions are fast, can be automated, and generally do not require pretreatment of biological material. Based on these advantages, they are widely used. On the other hand, they are susceptible to analytical interference that can lead to inaccurate results. These factors include the presence of anti-mouse antibodies, causing false positive (or sometimes false negative) results. Although the anti-mouse antibodies over many decades have been repeatedly identified to be the causative source but due to the rarity of such encounters they remain insufficiently considered. Here we show a case, a 45 year-old female who was mis-diagnosed with pregnancy due to falsely elevated human chorionic gonadotropin (hCG) due to anti-mouse antibodies. This led to the patient undergoing two ultrasound examinations and laparoscopy before the hCG was repeated on alternative assays which showed negative results, preventing the patient from methotrexate treatment. Here we describe the details of the case, outline the assay principal, supporting the finding from literature and outlining a process on how to identify such interferences in timely manner.

• MeSH
• choriogonadotropin * MeSH
• falešně pozitivní reakce MeSH
• lidé středního věku MeSH
• lidé MeSH
• protilátky * MeSH
• těhotenství MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Elevated levels of nausea and vomiting in pregnancy (NVP) and disgust sensitivity have been observed in the first trimester and both are thought to have a protective function for the mother and her fetus. Their aetiology is not clear, however, with previous studies attributing elevated NVP and disgust to various factors including endocrine changes, immunological changes, and psychological variables. To date, no study has directly assessed the relationship between disgust and NVP. Here, we prospectively collected two independent samples (S1 and S2; n1 = 201, n2 = 391) of women in the first trimester of pregnancy, who completed the Index of Nausea, Vomiting, and Retching and the Disgust Scale-Revised. We also measured free β-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein A (PAPP-A) in maternal serum. Our results did not confirm any association between NVP and disgust; in addition, they indicate that NVP and disgust may have different proximate causes. Disgust sensitivity was significantly negatively correlated with free β-hCG and (only in S1) with PAPP-A. In contrast, NVP was significantly positively associated with free β-hCG levels and (only in S1) with PAPP-A. While low hCG levels seem to be an important indicator for activation of the behavioral immune system in the first trimester, increased hCG levels play a role in stronger symptoms of NVP, a result consistent with previous studies. Levels of PAPP-A are likely part of a larger network of immunological and endocrine responses and do not appear to provide sufficient information for predicting women's NVP and disgust sensitivity.

• MeSH
• biologické markery MeSH
• komplikace těhotenství * MeSH
• lidé MeSH
• lidský choriogonadotropin, beta podjednotka MeSH
• nauzea etiologie   MeSH
• odpor * MeSH
• první trimestr těhotenství MeSH
• těhotenský plazmatický protein A metabolismus   MeSH
• těhotenství MeSH
• zvracení etiologie   MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Cíl: V České republice lze ženě uměle ukončit těhotenství farmakologickou metodou (UUT-F) v I. trimestru do 49. dne sekundární amenorey. Cílem studie je analýza významu stanovení lidského choriového gonadotropinu (hCG) v séru/moči a ultrazvukového (UZ) vyšetření při diagnostice těhotenství a hodnocení výsledku UUT-F. Metodika: V letech 2017 a 2018 bylo na našem pracovišti provedeno UUT-F celkem u 109 žen sekvenčním podáním mifepristonu (600 mg perorálně) a misoprostolu (400 mcg perorálně). Stanovení hCG v séru/moči a UZ vyšetření byly provedeny při diagnostice těhotenství i hodnocení výsledku UUT-F. Výsledky: Při diagnostice těhotenství byla pozitivní a středně silná korelace mezi hCG v séru a průměrem gestačního váčku v dutině děložní (GS – gestational sac) (r = 0,711; p < 0,0001) i velikostí zárodku v dutině děložní (CRL – crown-rump length) (r = 0,605; p < 0,0001). Délka těhotenství byla 42–49 dní amenorey (průměr 45,6; medián 45), ženy byly ve věku 16–44 let (průměr 29,4; medián 29). Při kontrolním vyšetření po UUT-F byla u 13,8 % žen (15/109) hodnota hCG v séru > 1 000 IU/l a u 17,4 % (20/109) byl pozitivní low sensitivity urine pregnancy test (LSUP test). UZ vyšetření diagnostikovalo „Pokračující těhotenství“ u pěti žen a zamlklé těhotenství u jedné ženy (hCG v séru bylo vždy > 1 000 IU/l a LSUP test byl vždy pozitivní). U 5,5 % žen (6/109) byla provedena následná chirurgická intervence vč. „Pokračujícího těhotenství“ (n = 5); u zamlklého těhotenství (n = 1) byl podán další misoprostol a chirurgickou intervenci nebylo nutné provést. Závěr: Při diagnostice těhotenství je pozitivní a středně silná korelace mezi hCG v séru a CRL. Při kontrolním vyšetření po UUT-F umožní negativní LSUP test spolehlivě vyloučit pokračující těhotenství. V případě pozitivního LSUP testu by mělo být provedeno ultrazvukové vyšetření, nicméně chirurgická intervence by neměla být indikována pouze na základě rozšíření dutiny děložní.

Objective: In the Czech Republic, it is possible, to carry out Medical Termination of Pregnancy (MToP) in the 1st trimester up until the 49th day of secondary amenorrhea. The aim of the study is to analyse the significance of serum/urine human chorionic gonadotropin (hCG) assessment and ultrasound (US) examination in pregnancy diagnosis and MToP follow-up. Methods: In 2017–2018, MToP was carried out in a total of 109 women by administering a combination of mifepristone (600 mg orally) and misoprostol (400 mcg orally). Serum/urine (LSUP – low sensitivity urine pregnancy test) hCG assessment and US examination were performed at pregnancy diagnosis and MToP follow-up. Results: At pregnancy diagnosis, there was a positive and medium strong correlation between serum hCG and size of the gestational sac – GS (R = 0.711; P < 0.0001) and crown-rump length of the embryo – CRL (R = 0.605; P < 0.0001). Gestational age was 42–49 days (average 45.6, median 45 days), the women were 16–44 years of age (average 29.4, median 29 years). In MToP follow-up, serum hCG level was > 1,000 IU/L in 13.8% of women (15/109) and a positive LSUP test in 17.4% (20/109). US examination diagnosed ongoing pregnancy in five women and missed abortion in one woman (serum hCG was always > 1,000 IU/L and LSUP test was always positive). In 5.5% of women (6/109), a subsequent surgical intervention was carried out including those with ongoing pregnancy (N = 5); missed abortion (N = 1) was treated by additional misoprostol, where surgical intervention was not necessary. Conclusion: At pregnancy diagnosis, there is a positive and medium strong correlation between serum hCG and CRL. In MToP follow-up, a negative LSUP test enables reliable exclusion of ongoing pregnancy and missed abortion. In case of a positive LSUP test, US examination should be performed; however, surgical intervention should not be indicated solely on the basis of uterine cavity dilatation.

• MeSH
• abortiva aplikace a dávkování   MeSH
• choriogonadotropin krev   MeSH
• dospělí MeSH
• gestační váček MeSH
• indukovaný potrat * metody   MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• prospektivní studie MeSH
• první trimestr těhotenství MeSH
• statistika jako téma MeSH
• těhotenství MeSH
• temenokostrční délka MeSH
• ultrasonografie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• těhotenství MeSH
• ženské pohlaví MeSH

Cíl: Shrnutí nových poznatků v oblasti implantace embrya v závislosti na kvalitě endometria. Metodika: Rešerše literatury publikované do srpna 2022 v databázích WoS, Scopus, PubMed/Medline se zaměřením na „endometrial receptivity“, „polycystic ovary syndrome“, „endometriosis“, „SARS-CoV-2“. Výsledky: Receptivní stav endometria je výsledkem fyziologické remodelace, činnosti imunity modulované mikrobiomem. Tuto rovnováhu narušují myomy, polypy, saktosalpingy, adenomyóza, endometrióza, syndrom polycystických vaječníků, infekce. Diskutuje se dopad infekce SARS-CoV-2. Pro úspěšnou implantaci je klíčové časování embryotransferu. Konvenčně se pro tyto účely využívá ultrazvuk. Ve specifických případech hysteroskopie a biopsie endometria. Vzorek se hodnotí histologicky, imunohistochemicky, vyšetřuje se mikrobiom anebo transkriptom. Jako podpora implantace jsou využívány gestageny, u syndromu polycystických ovarií metformin. U opakovaného selhání implantace intrauterinní infuze mononukleárů, plazmy bohaté na destičky, subkutánní aplikace granulocyty stimulujícího růstového faktoru, intravenózní podání atosibanu, intrauterinní aplikace choriogonadotropinu. Závěr: Nejnovější výzkumy na poli transkriptomiky, proteomiky a reprodukční imunologie hlouběji odkrývají implantaci a otvírají novou etapu asistované reprodukce.

Objective: A summary of new knowledge on embryo implantation in dependence on quality of the endometrium. Methods: Literature review from August 2022 of the relevant publications in Web of Science, Scopus and PubMed/Medline databases, focused on “endometrial receptivity”, “polycystic ovary syndrome”, “endometriosis”, “SARS-CoV-2”. Results: The receptive state of the endometrium is a result of physiological remodeling and immune system activity modulated by the microbiome. This balance can be disturbed by myomas, polyps, sactosalpings, adenomyosis, endometriosis, polycystic ovary syndrome, infections. The effect of SARS-CoV-2 infection is being discussed. For a successful implantation, timing of transfer is crucial. The ultrasound examination is used conventionally. In specific cases, hysteroscopy and endometrium biopsy are recommended. Histological and immunohistochemical evaluation is performed together with examination of microbiome or transcriptome. To support the implantation, gestagenes are used, or metformin in the patients with polycystic ovary syndrome. In cases of a repeated implantation failure, the intrauterine infusion of mononuclear cells or platelet rich plasma is used, subcutaneous application of granulocyte colony stimulating growth factor, intravenous application of atosiban or intrauterine application of human chorionic gonadotropin. Conclusion: Recent research in the field of transcriptomics, proteomics and reproductive immunology uncovers the process of implantation more deeply and opens a new stage of the assisted reproduction.

• MeSH
• choriogonadotropin MeSH
• COVID-19 metabolismus   MeSH
• endometrióza MeSH
• implantace embrya * fyziologie   MeSH
• lidé MeSH
• syndrom polycystických ovarií MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• přehledy MeSH

• MeSH
• choriogonadotropin analýza   MeSH
• gestační trofoblastická nemoc * diagnóza   epidemiologie   komplikace   MeSH
• lidé MeSH
• nádory mozku diagnostické zobrazování   sekundární   MeSH
• paréza diagnóza   etiologie   MeSH
• staging nádorů MeSH
• trofoblastické nádory sekundární   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky 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