A review of factors influencing the implantation of euploid blastocysts after in vitro fertilization

This is a comprehensive review of the current literature addressing factors that are involved in successful implantation euploid blastocysts. It includes analysis published studies on laboratory may impact performance blastocysts, including morphology, day biopsy, and rebiopsy. Preexisting underlying patient outcome embryo transfer (ET) blastocysts also explored, body mass index endocrine abnormalities. The role uterine environment its potential reviewed, endometrial thickness pattern, architecture, adenomyosis. Finally, stimulation methods preparation for frozen ET analyzed. Euploid embryos appear to have similar outcomes regardless maternal age (up approximately 40 years), frozen-thawed protocol (in ovulatory women), or trigger type, culture conditions. Decreased rates be expected from with poorer those biopsied 7, twice biopsied/frozen, after difficult ET. Patients very advanced age, high index, adenomyosis, polycystic ovary syndrome, possibly methylenetetrahydrofolate reductase carriers at higher risk failure early pregnancy loss. only applies who able produce There lack evidence support any interventions subsequently increase implantation. DIALOG: You can discuss this article authors other readers https://www.fertstertdialog.com/posts/xfnr-d-21-00065Essential points•To choose optimal blastocyst single transfer, embryo’s morphological grade, status zona pellucida, development should considered.•Synchrony between endometrium appears play key blastocysts.•Patient such as weight thyroid hormone addressed optimize healthy blastocyst.•The choice vitro fertilization protocols does not significant blastocysts.•The timing, size, number biopsies an blastocyst. https://www.fertstertdialog.com/posts/xfnr-d-21-00065 •To Live birth (IVF) dependent into receptive endometrium. In general, 3 contribute implantation: quality; receptivity; technique. Of these factors, quality arguably most important perhaps least well understood point time. With advent preimplantation genetic testing aneuploidy (PGT-A), ploidy determined accuracy. Having correct complement chromosomes necessary, but sufficient, criterion resulting live and, thus, good proxy determining whether IVF treatment will successful. However, roughly one third deemed high-enough do implant successfully. A variety been investigated predict success (Table 1). Some previous biased by varying multiple untested embryos, where embryonic cannot ruled out factor limited success. By controlling ploidy, variables systematically studied determine which better successfully implants. At level, expansion stage, timing predictive. Even if has result birth, ability implant, (age, [BMI], general health status), paternal (age sperm quality), (endometrial thickness, compaction pathology), medication protocols, explores retrospective prospective included trophectoderm biopsy PGT-A examines many studying clinicians counsel patients selection elective (eSET).Table 1Summary subcategory influencing blastocysts.CategorySubcategorySummary statementEmbryonic factorsBlastocyst morphologyThere fair suggest increasing grade ICM positive blastocysts.Blastocyst stageThere nonfully hatched chance than fully blastocysts.Timing formationThere 7 lower 5 6 blastocysts.Mitochondrial DNAThere insufficient mitochondrial DNA content potential.Uterine factorsEndometrial appearanceThere start progesterone cycles impacts blastocysts.EndometritisThere chronic endometritis likelihood history recurrent failure, although further needed blastocysts.History cesarean sectionThere prior lowers rate transfer.Presence adenomyosis endometriosisThere presence endometriosis blastocysts.Arcuate uterusThere diagnosis arcuate uterus blastocysts.Ease transferThere blastocysts.Endometrial disruptionThere disruption before improve rates.IVF protocolsOvarian triggerThere ovarian type blastocysts.FET protocolsThere FET adjusting based receptivity blastocysts.Progesterone levelThere improved when level >20 ng/mL transfer.Being previously vitrified eggThere altered derived oocytes.Fresh vs. improvement vitrified-warmed compared fresh blastocysts.Patient factorsMaternal ageThere extremes negatively blastocysts.Paternal 41–50 years clinical blastocysts.Sperm fragmentationThere fragmentation euploidy outcomes.BMIThere increased BMI leads worse miscarriage decreased rates.MTHFR gene mutationThere MTHFR homozygosity rates.Vitamin D low vitamin levels undergoing transfer.TSHThere TSH <2.5 mIU/L transfer.Embryology protocolsTiming biopsyThere cleavage-stage rate, whereas blastocyst-stage same negative impact.Size larger size rates.Type mediaThere culturing sequential media over monophasic rates, progression improved.Culture temperatureThere lowering temperature 36°C 37°C rates.Dynamic static cultureThere dynamic yield culture.Number vitrification cyclesThere double blastocysts.Note: = index; deoxyribonucleic acid; transfer; inner cell mass; fertilization; reductase; thyroid-stimulating hormone. Open table new tab Note: Blastocyst grading/morphology widely used marker assess assist best transfer. morphology alone accurate enough reliably exclude aneuploid being transferred. study Capalbo et al. (1Capalbo A. Rienzi L. Cimadomo D. Maggiulli R. Elliott T. Wright G. al.Correlation standard observational two centers involving 956 screened blastocysts.Hum Reprod. 2014; 29: 1173-1181Crossref PubMed Scopus (290) Google Scholar) suggested was associated ongoing pregnancy; “poor”-quality fared just high-graded remember even were sufficient undergo survive warming finding challenged Irani (2Irani M. Reichman Robles Melnick Davis O. Zaninovic N. al.Morphologic grading influences rates.Fertil Steril. 2017; 107: 664-670Abstract Full Text PDF (77) Scholar). They found difference basis transferred Similar Scholar), grouped 4 categories (excellent, good, average, poor). Although 38 excellent transferred, resulted pregnancies significantly more often average- poor-quality (ongoing excellent, 84.2%, 55.8%, poor, 35.8%). note, randomized. had did good-quality available. Hence, it possible some diminished oocyte and/or quality, contributed poor-quality, Another criticism mosaicism segmental imbalance. array comparative genomic hybridization (aCGH), validated detection abnormalities next-generation sequencing (NGS). Next-generation acid (DNA) technology allows rapid, low-cost, high-throughput genome. using NGS, Gonzalez (3Viñals X. Odia Naja Serhal P. Saab W. Seshadri S. al.Euploid irrespective their NGS-(PGT-A) patients.J Assist Reprod Genet. 2019; 36: 1623-1629Crossref (12) no statistically implantation, pregnancy, 179 thawed because scores prioritized cases >1 available largest cohort date, Nazem (4Nazem T.G. Sekhon Lee J.A. Overbey J. Pan Duke al.The correlation human blastocysts.Reprod Biomed Online. 38: 169-176Abstract (26) 2,236 ETs 1,629 couples. Embryonic 1 2 different PGT platforms, NGS quantitative polymerase chain reaction (PCR), relatively insensitive imbalances. affected platform used. Grading (ICM) reliable predictor outcomes. Grade 55.6% 32.3% C (P<.001). Their results grading, particularly composite predictive pregnancy/live ETs. These investigators concluded guide among embryos. Future sample elucidate predicting Other consider inherent variability subjectivity grading. considered another. To true effect outcomes, randomized controlled trial (RCT) would random “best” morphology. control possibility generate AA likely carry prognosis grades. As now, still provide guidance supernumerary maximize (FET). Extended PGT-A, enhance developed embryo. Without protection vulnerable trauma during cryopreservation, warming, Concerns regarding survival extrapolated mouse studies, bind surface cryostraw (5Zhu S.E. Sakurai Edashige K. Machida Kasai Cryopreservation zona-hatched blastocysts.J Fertil. 1996; 37-42Crossref (28) seen Rodriguez-Purata (6Rodriguez-Purata Gingold Whitehouse Slifkin Briton-Jones C. al.Hatching correlated chromosomally 2016; 31: 2458-2470Crossref (11) catheter retention 808 PCR-tested 46% hatched. Fully retained catheter, rates. biochemical loss similar, trend toward observed center (720 hatched, PCR- NGS-tested embryos) within pellucida (odds ratio [OR], 1.6; 99% confidence interval, 1.2–2.2) consistent data (7Ahlström Westin Wikland Hardarson Prediction pre-freeze post-thaw morphology.Hum 2013; 28: 1199-1209Crossref (64) Scholar, 8Hill M.J. Richter K.S. Heitmann R.J. Graham J.R. Tucker DeCherney A.H. al.Trophectoderm predicts single-blastocyst transfers.Fertil 99: 1283-1289.e1Abstract (118) 9Du Q.Y. Wang E.Y. Huang Y. Guo X.Y. Xiong Y.J. 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