The increased interest in assisted reproduction through in vitro fertilization (IVF) leads to an urgent need to identify biomarkers that reliably highly predict the success of pregnancy. Despite advances in diagnostics, treatment, and IVF approaches, the 30% success rate of IVF seems insurmountable. Idiopathic infertility does not have any explanation for IVF failure especially when a patient is treated with a healthy competitive embryo capable of implantation and development. Since appropriate intercellular communication is essential after embryo implantation, the emergence of the investigation of embryonic secretome including short non-coding RNA (sncRNA) molecules is crucial. That's why biomarker identification, sncRNAs secreted during the IVF process into the blastocyst's cultivation medium, by the implementation of artificial intelligence opens the door to a better understanding of the bidirectional communication between embryonic cells and the endometrium and so the success of the IVF. This study presents a set of promising new sncRNAs which are revealed to predictively distinguish a high-quality embryo, suitable for an embryo transfer in the IVF process, from a low-quality embryo with 86% accuracy. The identified exact combination of miRNAs/piRNAs as a non-invasively obtained biomarker for quality embryo determination, increasing the likelihood of implantation and the success of pregnancy after an embryo transfer.
Cieľ: Cieľom štúdie bolo vyhodnotiť prediktívnu hodnotu koncentrácie ľudského choriového gonadotropínu (hCG) 14. a 16. postovulačný deň po embryotransfer/kryoembryotransfere ako aj dynamiky vzostupu tejto koncentrácie vzhľadom na výsledok tehotnosti. Súbor a metodika: Retrospektívne boli na skupine 130 pacientok s potvrdenou graviditou po embryotransfere/kryoembryotransfere regresnou analýzou vyhodnotené vstupné parametre (hCG D14, hCG D16, D16–D14, D16/D14 a splnenie podmienky aspoň 2,5násobného vzostupu hCG D16 oproti hCG D14) vo vzťahu ku výstupným parametrom (biochemická gravidita, klinická gravidita, klinická gravidita ukončená potratom do 12. týždňa tehotnosti, klinická gravidita ukončená pôrodom). Výsledky: Jednorazové koncentrácie hCG D14 a D16, ako aj rozdiel týchto koncentrácií bol štatisticky signifikantným ukazovateľom predikcie biochemickej tehotnosti (p = 0,000215, p = 0,000227 a p = 0,000421). Podiel koncentrácií hCG D16 a D14 nevykazoval štatistickú významnosť ako prediktívny ukazovateľ ukončenia tehotnosti v štádiu biochemickej gravidity. Ani jeden zo sledovaných vstupných markerov sa nepotvrdil ako štatisticky významný marker pre predikciu spontánneho potratu v celej skupine pacientok. Avšak v skupine potvrdených klinických gravidít bola ako pozitívny prediktor progresie tehotnosti až do pôrodu potvrdená tak sérová koncentrácia hCG D16 (p = 0,0248), ako aj rozdiel koncentrácií D16–D14 (p = 0,0185). Násobok tohto vzostupu ani pri týchto parametroch nebol štatisticky významný. Ani pri jednom sledovanom výstupnom parametri sa nepotvrdila štatistická významnosť dosiahnutia aspoň 2,5-násobku sérovej koncentrácie hCG D16 oproti D14. Záver: Jednorazové koncentrácie hCG sú dobrým prognostickým faktorom pre predikciu výsledku gravidity, stanovenie cut-off hranice je však limitované interlaboratórnou odchýlkou, ako aj datovaním odberu hCG. Preto sú aj výsledky jednotlivých štúdií v klinickej praxi ťažko použiteľné. Dynamika sledovania koncentrácií hCG sa javí ako spoľahlivejší prediktor výsledku tehotnosti. V našom súbore sme potvrdili štatistický význam rozdielu koncentrácie hCG 16. a 14. postovulačný deň nielen pre predikciu biochemickej tehotnosti, ale aj ako prediktora progresie klinickej tehotnosti do pôrodu. Na stanovenie optimálnych hodnôt tohto rozdielu je potrebné vyhodnotenie väčšieho súboru pacientov. Naopak, štatistický význam podielu koncentrácií hCG medzi 16. a 14. postovulačným dňom nebol potvrdený.
Objective: The aim of the study was to evaluate the predictive value of the human chorionic gonadotropin (hCG) concentration on the 14th and 16th post-ovulation day after embryo transfer/cryoembryo transfer as well as the dynamics of its increase with respect to the outcome of pregnancy. Materials and methods: In total, 130 embryo transfers and cryoembryo transfers in women aged 22 to 38 years who experienced a single embryo transfer or single cryoembryo transfer with confirmed pregnancy (hCG level over 15 IU/l on 14th post-ovulation day – D14) were selected. The input parameters (hCG D14, hCG D16, hCG D16-D14, hCG D16/D14 and positivity of at least 2.5-fold increase in hCG D16 compared to hCG D14) were evaluated by regression analysis in relation to the outcome parameters (biochemical pregnancy, clinical pregnancy, clinical pregnancy terminated by abortion up to 12 weeks of gestation, clinical pregnancy terminated by childbirth). Results: Single concentrations of hCG D14 and D16, as well as the difference between these concentrations, were a statistically significant indicator of the prediction of biochemical pregnancy (P = 0.000215, P = 0.000227 and P = 0.000421). Contrary to expectations, the proportion of hCG D16 and D14 concentrations did not show statistical significance for either parameter, as well as the fulfilment of the condition of at least a 2.5fold increase in hCG D16 compared to D14. None of the studied input parameters was confirmed as a statistically significant marker for the prediction of miscarriage in the whole group of patients. However, in the group of confirmed clinical pregnancies, the serum concentration of hCG D16 (P = 0.0248) and the difference between concentrations D16 and D14 (P = 0.0185) were confirmed as a positive predictor of the progression of pregnancy until delivery. Conclusions: Single hCG concentrations are a good prognostic factor for predicting the outcome of pregnancy, but the determination of the cut-off limit is limited by inter-laboratory deviation as well as by timing of blood collection for hCG determination on the exact post-ovulatory day. The results of individual studies are therefore difficult to use in clinical practice. The dynamics of hCG concentrations appear to be a more reliable predictor of pregnancy outcome. In our cohort, we confirmed the statistical significance of the difference in hCG concentration between the 16th and 14th post-ovulation day not only for the prediction of biochemical pregnancy, but also as a predictor of the progression of clinical pregnancy into childbirth. To determine the optimal values of this difference, it is necessary to evaluate a larger group of patients. Conversely, the statistical significance of the proportion of hCG concentrations between the 16th and 14th post-ovulation day was not confirmed.
