Survival of Single Immediate Implants and Reasons for Loss: A Systematic Review

Abstract

Background: Immediate implant placement (IIP) or Type I implants have become more attractive than conventional implant placements as it reduces the number of surgical procedures and allows faster delivery of the final restoration compared to conventional implant placements. However, the survival of Type I implants varies depending on multiple factors. Purpose: To evaluate the survival rate of Type I implants, and to describe the factors influencing their failure. Materials and methods: A developed search strategy was applied to identify randomised controlled trials on single-unit immediate implants including at least six human participants with a minimum follow-up time of 12 months and published between 1 January 1999 and 1 January 2020 in several databases. The data were extracted independently using validated data extraction forms. Information on survival rates, number of implants placed, loading protocols, setting of the study, location of implants in the jaw, antibiotic protocol, grafting methods, and implant geometry were obtained and assessed. Results: Twenty-six randomised controlled trials with an average follow-up time of 24 months (range = 12–120 months) were included and analysed to give a survival rate ranging between 83.7 and 100%. Fifteen studies reported implant failures, of which twelve reported early losses (loss before definitive restoration). Nine early losses were due to lack of osseointegration, two did not report the reason for implant failure, and one was reported as iatrogenic. Of the eleven studies with 100% survival rates, the common trend observed was the use of titanium implants and an antibiotic regimen using amoxicillin. Conclusions: The survival rate for immediate single implant placement ranged from 83.7 to 100%. Implant failure was not consistently reported and when reported, failure due to lack of osseointegration prior to placement of the definitive restoration was the most common descriptor. Other attributed reasons included infection abscess, mobility after immediate loading, and iatrogenic complications.

1. Summary Box

• What is known:

There are several systematic reviews on the survival of immediate implants which did not differentiate between single-unit and multiple-unit implants, or between different loading protocols. These reviews also have limitations, such as inclusion of non-randomised controlled trials and no risk of bias assessment.

• What this study adds:

The current review was designed to overcome the limitations of these previous systematic reviews and to update the current knowledge on the survival rate of single-unit immediate implants. This study suggests that immediate implants can be a predictable procedure with high survival rates based on the most current randomised controlled trials.

2. Introduction

Implants are an attractive treatment option for single tooth replacement, especially when traditional restorative options may be too destructive or inconvenient for the patient, such as a conventional 3-unit, cantilevered, or resin-bonded fixed partial denture, or a removable partial denture. Despite the increasing popularity of implants, they require complex, multidisciplinary treatment planning and strict inclusion criteria [1].

Conventional implant placement typically requires longer periods of healing before the final restoration can be placed, which may increase the psychological impact of tooth loss [2]. Type I or immediate implant placement (IIP), therefore, has become the more appealing option for both patients and dentists due to the reduced number of surgical procedures and, hence, shorter treatment time [1]. However, IIP should be based on case selection as successful placement is not always guaranteed [1]. Primary stability, which is paramount in the success of dental implant treatment is often difficult in IIP due to the lack of hard tissue immediately post-extraction. In order to achieve primary stability, a 3–5 mm apical, palatal, and intraradicular bone is needed [2]. Furthermore, bony defects and unfavourable bony morphology post-extraction present a challenge to osseointegration [3]. When an implant fails to osteointegrate, its removal can cause trauma. As implants do not display bundle bone, the remaining defect after removal of failed implants do not behave like post-extraction sockets [4]. Therefore, a re-attempt at implant placement may not be possible and the patient may be left with less or even no option to replace their missing dentition [5,6].

The survival of an implant is defined as the presence of the implant upon recall examination, despite its conditions. Conversely, implant failure is the absence of the implant on recall examination. These definitions are derived from the Third International Team of Implantology (ITI) consensus meeting [7]. Implant failure can be further grouped into four main reasons: biological, mechanical, iatrogenic, or inadequate patient adaptation requiring removal of implants. Biological issues are related to osseointegration and can be classified into early and late loss depending on whether it was lost before or after implant loading, respectively [8].

There are several systematic reviews on the survival of immediate implants with different independent variables applied across a range of implant systems from numerous manufacturers [9,10,11,12,13,14,15]. Some of these studies did not differentiate between single-unit and multiple-unit implants, or between different loading protocols. Some of these reviews also included non-randomised controlled trials and did not investigate the risk of bias (refer to

Table 1. List of published systematic reviews on immediate implants and their limitations.

Study	Survival Rate (Follow-Up Period)	Limitations
Atieh et al., 2010 [9]	94–100% (6–36 months)	Included studies with follow-up of less than 1 year Published 10 years ago Included non-randomised control trials Did not assess for bias risk for the RCTs included Inclusion criteria for follow up was only 6 months
Chen et al., 2014 [10]	N/A (1–3 years)	Did not investigate and define survival, success, and failure Included non-randomised controlled trials
Cosyn et al., 2019 [11]	94.9% (12–96 months)	Included non-randomised controlled studies Small number of studies included (n = 8) 7 out of 8 studies had high risk of bias Did not investigate the implant loading protocol
Lang et al., 2012 [12]	98.4% (2 years) 97.5% (4 years)	Included multiple-unit IIP Included non-randomised controlled trials Published 8 years ago
Mello et al., 2017 [13]	95.2% (6 months)	Did not define survival Included studies with follow-up of less than 12 months Included multiple-unit implants Included non-randomised controlled studies Did not define survival
Pigozzo et al., 2018 [14]	95% (1–5 years)	Small sample size (n = 5) Did not define survival
Pjetturson et al., 2007 [15]	92–99% (3 years)	Included multiple-unit Implants Did not mention whether the implants were immediate or delayed placements Did not define survival Included non-randomised controlled trials Did not investigate loading protocols Did not assess bias risk

). The current review is designed to overcome the limitations of these previous systematic reviews. The objective of this systematic review is to evaluate the survival rate of single-unit immediate implants using recent randomised controlled trials, and to establish a link between the reasons for failure and factors that may influence its survival.

3. Materials and Methods

This systematic review was registered as a protocol in the International Prospective Register of Systematic Reviews (PROSPERO) platform (CRD42020173150), and the reporting was carried out following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [16].

3.1. Search Strategy

A detailed search strategy was used for the PubMed database to identify all articles published between 1 January 1999 and 1 January 2020 in relation to the stated aims of this review. In addition, a manual search of Clinical Oral Implants Research and the European Journal of Oral Implantology was attempted to identify any relevant studies. The reference list from the included studies was also screened for further inclusions into this study.

Focused question: what is the survival rate of single-unit immediate implant and what is the reason for implant failure?

The following PICO strategy was designed to select the studies to be included in this review [17]:

Participants: Subjects requiring a single implant in the maxillary and mandibular areas.

Intervention: Implant placement using the immediate placement protocol (Type 1).

Comparison: Delayed implant treatment protocols (Type 4) used for the replacement of a single tooth in the maxillary and mandibular region.

Outcomes: Implant survival, implant failure, and the reasons for failure.

Eligibility criteria:

For a study to be included it must meet the following inclusion criteria:

• Randomised controlled trial;
• Study included a minimum of six human subjects or more, including split mouth studies;
• Used single-unit immediate implants;
• Minimum follow-up time of one year;
• Full-text study published in English

3.2. Study Selection

After the initial electronic search of titles by two authors (N.K. and B.K.), the titles and abstracts of all the studies identified via electronic searches were independently scanned by two reviewers (N.K. and L.A.M.). The next step was to review all selected abstracts to determine selection of full-text articles after applying the inclusion criteria. The full texts of all studies of possible relevance were then obtained for independent review and assessment by the two reviewers. Disagreements among reviewers were resolved by discussion. All studies meeting the inclusion criteria then underwent data extraction. Studies rejected at this or subsequent stages were removed and the reasons for exclusion were recorded (Figure 1).

3.3. Data Extraction

The data were independently extracted by a group of seven review authors (N.K., W.T., P.S., P.G.S., J.G., C.T., D.C.) using validated data extraction forms. Any discrepancies between the reviewers were resolved by discussion and consensus after consultation with the other author (L.A.M.).

The implants in the included studies were grouped into four categories based on implant placement and loading protocol: immediate placement and immediate loading (IPL); immediate placement and immediate restoration with a non-occluding provisional crown (IPR); immediate placement and delayed restoration, which includes both early and conventional loading (IPDL); and delayed placement, regardless of loading technique (DP). This review classifies implant placement and implant loading protocols according to the Third International Team of Implantology (ITI) Consensus conference in 2003 [18,19].

The information on survival rates, number of implants placed, loading protocols, setting, location of implants in the jaw, antibiotic protocols, grafting methods, and implant systems were obtained (see Table 2). These parameters were assessed to determine if they influenced the survival rates reported by the studies.

3.4. Risk of Bias Assessment

The quality of the included studies was assessed by six independent reviewers (W.T., P.S., P.G.S., J.G., C.T., D.C.) following the Cochrane Risk of Bias tool for randomised controlled trials [20]. This tool encompasses seven criteria: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias. All studies were judged against these criteria as having low, unclear, or high risk of bias. The overall risk of bias was low if all criteria were considered to be at low risk of bias, unclear if there was at least one criterion with unclear risk of bias, and high if there was at least one criterion with a high risk of bias.

[Diagram is in a PDF file as requested by CIDRR author guidelines.]

Table 2. Summary table of included studies.

Study	Group	Settings	Follow-Up Time (Months)	Imp Survival % (IPL)	Imp Survival % (IPR)	Imp Survival % (IPDL)	Imp Survival % (DP)	Reason for Implant Failure	Antibiotics	Bone Grafting	Implant System/ Platform/ Geometry	Location in Jaw: No. of Imps
Canullo et al., 2009/2017 [21,22]	IPR	Mc (2 PP)	25, 120	N/A	100	N/A	N/A	N/A	Augmentin: 1 h pre-op and 6 days post-op	Bovine bone matrix (Bio-Oss Collagen, Geistlich-Pharma, Wolhusen, Switzerland)	Global imp, 5.5 mm, 13 mm	Mx: 19
Tallarico et al., 2016/2017 [23,24]	IPDL vs. DP	PP	12 (6 months post loading)	N/A	N/A	100	100	N/A	Amoxicillin/Clindamycin: 1 h pre-op	Corticocancellous heterologous bone (OsteoBiol Gen-Os; Tecnoss srl, Giaveno, Italy)	Osstem TSIII Ultra-Wide 7 mm-diameter. 8.5 mm long (n = 4), 10 mm long (n = 18), and 11.5 mm long (n = 2)	Mx: 12 Md: 12
Cannizzaro et al., 2010 [25]	IPL, IPR vs. DP	Mc (4 PP)	36	40	80	N/A	97	1 IPL imp failed as bruxism habit was only diagnosed after failure; 4 imps failed to osseointegrate	Amoxicillin/Clindamycin: pre-op and 6 days post-op if graft was performed	Autogenous bone or bone substitutes	Z-Look3 zirconia implants, 3.25–6 mm, 10–15.5 mm	Mx: 29 Md: 11
Shibly et al., 2012 [26]	IPL vs. IPDL	U	3, 6, 12	96.6	N/A	93.3	N/A	1 imp failed due to mobility; 1 imp failed from acute infection 3 months after placement; 1 imp failed with no reason for implant failure given	Amoxicillin: 2 days pre-op and 10 days post-op	Sterile demineralized freeze-dried bone (DFDBA)—OraGRAFT, LifeNet Health, Virginia Beach, VA, USA.	NobelReplace™ Straight Groovy, with TiUnite® surface, Nobel Biocare	Mx: 36 Md: 19
Block et al., 2009 [27]	IPR vs. IPDL	Not specified	1, 2, 3, 4, 10, 16, 22 28	N/A	84.6	96.6	N/A	5 implants failed with no reason given	Cephalosporin: 7 days post-op	Human mineralized bone allograft	3i, 11.5–13 mm	Mx: 55
Canullo et al., 2010 [28]	IPR	Mc (3 PP)	36	N/A	100	N/A	N/A	N/A	Augmentin: 1 h pre-op	Nano-structured hydroxyapatite (Sintlife, Faenza, Italy)	Global Implant, 5.5 mm, 13 mm	Mx: 32
De Rouck et al., 2009 [29]	IPR vs. IPDL	U	12	N/A	96	92	N/A	1 imp failed due to mobility at 1 month; 2 imps failed due to mobility and pain at 3 months	Amoxicillin: 1 h pre-op and 5 days post-op	Bio-Oss®, (Geistlich Biomaterials, Mediplus, Rixensart, Belgium)	NobelReplace Tapered TiUnite, mostly diameter 4.3 mm, 16 mm	Mx: 30
Degidi et al., 2014 [30]	IPR	PP	24	N/A	100	N/A	N/A	N/A	Amoxicillin: 1 h pre-op and 5 days post-op	Not specified	Square-threaded, grit-blasted, and acid-etched implant with a tapered connection (ANKYLOS®, DENTSPLY)	Mx: 53
Esposito et al., 2015 [31]	IPR/IPDL vs. DP	Mc (3 PP)	12	N/A	96.3 Study did not give separate results for IPR and IPDL imp	100	1 imp failed due to mobility and pain at 1 month; 1 imp failed due to mobility at 4 months and imp crown was loose 20 days earlier		Amoxicillin/Clindamycin: 1 h pre-op and 6 days post-op if grafting was performed	Bio-Oss (Geistlich Pharma AG, Wolhusen, Switzerland)	Tapered titanium EZ Plus dental implants (MegaGen Implant, Gyeongbuk, Republic of Korea) with an internal connection, and RBM-treated surfaces, already provided with their definitive straight abutments	Mx: 106
Felice et al., 2015 [32]	IPR/IPDL vs. DP	Mc (4 PP)	4, 12	N/A	92 Study did not give separate results for IPR and IPDL imp	100	2 imps failed with unpleasant sensation/pain and mobility after 2 months after loading		Amoxicillin/Clindamycin: 1 h pre-op and 6 days post-op if grafting was performed	Frios Algipore (Dentsply, Friadent)	XiVE S plus (Dentsply Friadent, Mannheim, Germany) titanium, self-tapping, conical implants with an internal hexagon.Length choices: 8.0, 9.5, 11.0, 13.0, or 15.0 mm and diameters choices: 3.8, 4.5, or 5.5 mm	Mx: 48
Grandi et al., 2014 [33]	IPR	Mc	12	N/A	100	N/A	N/A	N/A	Augmentin/Clarithromycin: pre-op and 6/7 days post-op	Bio-Oss (Geistlich Bio-Oss, Geistlich Pharma, Wolhusen, Switzerland)	Tapered implants with internal connection and double acid-etched surface	Mx: 36
Migliorati et al., 2015 [34]	IPR	Not specified	0, 0.5, 12, 24	N/A	100	N/A	N/A	N/A	Amoxicillin/Clindamycin: 1 h pre-op	Bio-Oss (Geistlich Pharma North America, Inc., Princeton, NJ, USA)	Tapered Effect or Bone Level SLActive, Straumann Co., Basel, Switzerland	Mx: 48
Palatella et al., 2008 [35]	IPR vs. DP	U	24	N/A	100	N/A	100	N/A	Augmentin: 5 days post-op	-	Tapered effect (Institut Straumann AG, Waldenburg, Switzerland	Mx: 18
Pieri et al., 2011 [36]	IPR	U	12	N/A	97.4	N/A	N/A	1 imp failed with an abscess associated with a fistula	Augmentin: pre-op and 1 week post-op	Mixture of autogenous bone and Bio-Oss	Samo Smiler, root-shaped, microthreads in coronal portion, microporous and nanoroughened calcium and phosphorus-enriched titanium oxide surface. Platform switched when using Morse taper abutment	Mx: 38
Slagter et al., 2015 [37]	IPR vs. IPDL	U	12	N/A	100	100	N/A	N/A	Amoxicillin: 7 days pre-op	Mixture of autogenous bone and Bio-Oss	NobelActive, Nobel BIocare AB	Mx: 40
Yoshino et al., 2014 [38]	IPR	U	12	N/A	100	N/A	N/A	N/A	Did not specify antibiotic regime	BioOss, Osteohealth	Bone Level, Straumann USA. Dimensions: 3.3 mm, 14 mm (n = 5), 4.1 mm, 14 mm (n = 14), and 4.8 mm, 14 mm (n = 1)	Mx: 20
Zuiderveld et al., 2018 [39]	IPR	U	12	N/A	96.7	N/A	N/A	2 imps failed to osseointegrate	Amoxicillin/Clindamycin: 1 day pre-op and 7 days post-op	Bio-Oss and autogenous bone	Not specified	Mx: 60
Cecchinato et al., 2015 [40]	IPDL	Mc	36	N/A	N/A	98.9	N/A	1 imp was mobile at 16 weeks	No antibiotics used	Not specified	Either a cylindrical, 3.5 mm or 4.0 mm implant or a conical/cylindrical 4.5 or 5.0 mm implant (Osseospeed, DENTSPLY Implants)	Mx: 92
Cordaro et al., 2009 [41]	IPDL	PP	0, 1.5, 3, 6, 12, 18	N/A	N/A	96.6	N/A	1 imp failed due to prosthetic overload from under-trimming the removable prosthesis	No antibiotics used	Not specified	Tapered TE implants (Straumann)	Not specified (n = 30)
Cucchi et al., 2017 [42]	IPDL vs. DP	Mc	12, 36	N/A	N/A	95.5	100	2 imps failed to osseointegrate	Amoxicillin: 1 h pre-op and 6 h post-op	Resorbable B-tricalcium phosphate (Oxofix, Biotec BTK, Dueville, Vicenza, Italy, BTK Italy)	BT SAFE Bone Level—double lead threads with a hexagonal conical connection and integrated platform shifting	Mx: 25 Md: 24
De Angelis et al., 2011 [43]	IPDL	Mc (4 PP)	12	N/A	N/A	91.3	N/A	6 imps were mobile at abutment connection at 3–4 months; 1 imp failed after 3-month loading at 6–7 months after placement	Amoxicillin/clindamycin: 1 h pre-op and 6 days post-op	Endobon® (Biomet 3i), a bovine-derived, deproteinised, osteoconductive hydroxyapatite ceramic	NanoTite™ Tapered Certain® Prevail® titanium alloy (Ti6Al4V) implants (Biomet 3i, Palm Beach, FL, USA) with internal connection. Dual acid etched and then partially covered with nanoscale calcium phosphate crystals. Biomet 3i platform-switched abutments	Mx: 50 Md: 30
Koh et al., 2011 [44]	IPDL	U	12	N/A	N/A	95.5	N/A	1 imp failed with no reason given	Amoxicillin/Azithromycin: pre-op and 7/3 days post-op	Mixture of cortical and cancellous particulates allograft (MinerOss)	Tapered internal implant, BioHorizon, Birmingham, AL	Mx: 21
Prosper et al., 2003 [45]	IPDL	U	3, 6, 9, 12, 24, 36, 48	N/A	N/A	100	N/A	N/A	Augmentin: 6 days post-op	Synthetic hydroxyapatite (Biosite; Vebas, Milan, Italy)	Sandblasted, titanium (Bioactive Covering, Winsix, London, United Kingdom), self-threading cylindric screw, 5.9, 11, or 13 mm	Mx: 75 Md: 36
Urban et al., 2011 [46]	IPDL	Not specified	0.25, 12	N/A	N/A	83.7	N/A	15 imps failed to osseointegrate	Phenoxymethylpenicillin: 5 days pre-op	Autologous bone	Brånemark System, Mk III Groovy, Wide Platform implant (NobelBiocare, Göteborg, Sweden) with an external hex connection, 5.0 mm and a thread spacing of 0.8 mm	Mx: 45 Md: 47
Crespi et al., 2008 [47]	IPL vs. IPDL	U	24	100	N/A	100	N/A	N/A	Amoxicillin: 1 h pre-op and 1 week post-op	Not specified	40 outlink, Sweden & Marina, Pafova implants. 30 implants: 5 mm, 10 implants: 3.75 mm, 13 mm	Mx: 40
Van Nimwegen et al., 2018 [48]	IPR	U	12	N/A	96.7	N/A	N/A	2 imps failed to osseointegrate	Amoxicillin: pre-op and 7 days post-op	Mixture of autogenous bone and Bio-Oss	NobelActive (Nobel Biocare)	Mx: 60

IPR: immediately placed and restored, IPDL: immediately placed and delayed loading, IPL: immediately placed and loaded, DP: delayed placement, RCT: randomised control trial, PS-RCT: prospective randomised control trial, Mc: multicentre, PP: private practice, N/A: not applicable, RBM: resorbable blast media, IIP: immediately placed implants, Mx: maxillary, Md: mandibular.

Table 2. Summary table of included studies.

Study	Group	Settings	Follow-Up Time (Months)	Imp Survival % (IPL)	Imp Survival % (IPR)	Imp Survival % (IPDL)	Imp Survival % (DP)	Reason for Implant Failure	Antibiotics	Bone Grafting	Implant System/ Platform/ Geometry	Location in Jaw: No. of Imps
Canullo et al., 2009/2017 [21,22]	IPR	Mc (2 PP)	25, 120	N/A	100	N/A	N/A	N/A	Augmentin: 1 h pre-op and 6 days post-op	Bovine bone matrix (Bio-Oss Collagen, Geistlich-Pharma, Wolhusen, Switzerland)	Global imp, 5.5 mm, 13 mm	Mx: 19
Tallarico et al., 2016/2017 [23,24]	IPDL vs. DP	PP	12 (6 months post loading)	N/A	N/A	100	100	N/A	Amoxicillin/Clindamycin: 1 h pre-op	Corticocancellous heterologous bone (OsteoBiol Gen-Os; Tecnoss srl, Giaveno, Italy)	Osstem TSIII Ultra-Wide 7 mm-diameter. 8.5 mm long (n = 4), 10 mm long (n = 18), and 11.5 mm long (n = 2)	Mx: 12 Md: 12
Cannizzaro et al., 2010 [25]	IPL, IPR vs. DP	Mc (4 PP)	36	40	80	N/A	97	1 IPL imp failed as bruxism habit was only diagnosed after failure; 4 imps failed to osseointegrate	Amoxicillin/Clindamycin: pre-op and 6 days post-op if graft was performed	Autogenous bone or bone substitutes	Z-Look3 zirconia implants, 3.25–6 mm, 10–15.5 mm	Mx: 29 Md: 11
Shibly et al., 2012 [26]	IPL vs. IPDL	U	3, 6, 12	96.6	N/A	93.3	N/A	1 imp failed due to mobility; 1 imp failed from acute infection 3 months after placement; 1 imp failed with no reason for implant failure given	Amoxicillin: 2 days pre-op and 10 days post-op	Sterile demineralized freeze-dried bone (DFDBA)—OraGRAFT, LifeNet Health, Virginia Beach, VA, USA.	NobelReplace™ Straight Groovy, with TiUnite® surface, Nobel Biocare	Mx: 36 Md: 19
Block et al., 2009 [27]	IPR vs. IPDL	Not specified	1, 2, 3, 4, 10, 16, 22 28	N/A	84.6	96.6	N/A	5 implants failed with no reason given	Cephalosporin: 7 days post-op	Human mineralized bone allograft	3i, 11.5–13 mm	Mx: 55
Canullo et al., 2010 [28]	IPR	Mc (3 PP)	36	N/A	100	N/A	N/A	N/A	Augmentin: 1 h pre-op	Nano-structured hydroxyapatite (Sintlife, Faenza, Italy)	Global Implant, 5.5 mm, 13 mm	Mx: 32
De Rouck et al., 2009 [29]	IPR vs. IPDL	U	12	N/A	96	92	N/A	1 imp failed due to mobility at 1 month; 2 imps failed due to mobility and pain at 3 months	Amoxicillin: 1 h pre-op and 5 days post-op	Bio-Oss®, (Geistlich Biomaterials, Mediplus, Rixensart, Belgium)	NobelReplace Tapered TiUnite, mostly diameter 4.3 mm, 16 mm	Mx: 30
Degidi et al., 2014 [30]	IPR	PP	24	N/A	100	N/A	N/A	N/A	Amoxicillin: 1 h pre-op and 5 days post-op	Not specified	Square-threaded, grit-blasted, and acid-etched implant with a tapered connection (ANKYLOS®, DENTSPLY)	Mx: 53
Esposito et al., 2015 [31]	IPR/IPDL vs. DP	Mc (3 PP)	12	N/A	96.3 Study did not give separate results for IPR and IPDL imp	100	1 imp failed due to mobility and pain at 1 month; 1 imp failed due to mobility at 4 months and imp crown was loose 20 days earlier		Amoxicillin/Clindamycin: 1 h pre-op and 6 days post-op if grafting was performed	Bio-Oss (Geistlich Pharma AG, Wolhusen, Switzerland)	Tapered titanium EZ Plus dental implants (MegaGen Implant, Gyeongbuk, Republic of Korea) with an internal connection, and RBM-treated surfaces, already provided with their definitive straight abutments	Mx: 106
Felice et al., 2015 [32]	IPR/IPDL vs. DP	Mc (4 PP)	4, 12	N/A	92 Study did not give separate results for IPR and IPDL imp	100	2 imps failed with unpleasant sensation/pain and mobility after 2 months after loading		Amoxicillin/Clindamycin: 1 h pre-op and 6 days post-op if grafting was performed	Frios Algipore (Dentsply, Friadent)	XiVE S plus (Dentsply Friadent, Mannheim, Germany) titanium, self-tapping, conical implants with an internal hexagon.Length choices: 8.0, 9.5, 11.0, 13.0, or 15.0 mm and diameters choices: 3.8, 4.5, or 5.5 mm	Mx: 48
Grandi et al., 2014 [33]	IPR	Mc	12	N/A	100	N/A	N/A	N/A	Augmentin/Clarithromycin: pre-op and 6/7 days post-op	Bio-Oss (Geistlich Bio-Oss, Geistlich Pharma, Wolhusen, Switzerland)	Tapered implants with internal connection and double acid-etched surface	Mx: 36
Migliorati et al., 2015 [34]	IPR	Not specified	0, 0.5, 12, 24	N/A	100	N/A	N/A	N/A	Amoxicillin/Clindamycin: 1 h pre-op	Bio-Oss (Geistlich Pharma North America, Inc., Princeton, NJ, USA)	Tapered Effect or Bone Level SLActive, Straumann Co., Basel, Switzerland	Mx: 48
Palatella et al., 2008 [35]	IPR vs. DP	U	24	N/A	100	N/A	100	N/A	Augmentin: 5 days post-op	-	Tapered effect (Institut Straumann AG, Waldenburg, Switzerland	Mx: 18
Pieri et al., 2011 [36]	IPR	U	12	N/A	97.4	N/A	N/A	1 imp failed with an abscess associated with a fistula	Augmentin: pre-op and 1 week post-op	Mixture of autogenous bone and Bio-Oss	Samo Smiler, root-shaped, microthreads in coronal portion, microporous and nanoroughened calcium and phosphorus-enriched titanium oxide surface. Platform switched when using Morse taper abutment	Mx: 38
Slagter et al., 2015 [37]	IPR vs. IPDL	U	12	N/A	100	100	N/A	N/A	Amoxicillin: 7 days pre-op	Mixture of autogenous bone and Bio-Oss	NobelActive, Nobel BIocare AB	Mx: 40
Yoshino et al., 2014 [38]	IPR	U	12	N/A	100	N/A	N/A	N/A	Did not specify antibiotic regime	BioOss, Osteohealth	Bone Level, Straumann USA. Dimensions: 3.3 mm, 14 mm (n = 5), 4.1 mm, 14 mm (n = 14), and 4.8 mm, 14 mm (n = 1)	Mx: 20
Zuiderveld et al., 2018 [39]	IPR	U	12	N/A	96.7	N/A	N/A	2 imps failed to osseointegrate	Amoxicillin/Clindamycin: 1 day pre-op and 7 days post-op	Bio-Oss and autogenous bone	Not specified	Mx: 60
Cecchinato et al., 2015 [40]	IPDL	Mc	36	N/A	N/A	98.9	N/A	1 imp was mobile at 16 weeks	No antibiotics used	Not specified	Either a cylindrical, 3.5 mm or 4.0 mm implant or a conical/cylindrical 4.5 or 5.0 mm implant (Osseospeed, DENTSPLY Implants)	Mx: 92
Cordaro et al., 2009 [41]	IPDL	PP	0, 1.5, 3, 6, 12, 18	N/A	N/A	96.6	N/A	1 imp failed due to prosthetic overload from under-trimming the removable prosthesis	No antibiotics used	Not specified	Tapered TE implants (Straumann)	Not specified (n = 30)
Cucchi et al., 2017 [42]	IPDL vs. DP	Mc	12, 36	N/A	N/A	95.5	100	2 imps failed to osseointegrate	Amoxicillin: 1 h pre-op and 6 h post-op	Resorbable B-tricalcium phosphate (Oxofix, Biotec BTK, Dueville, Vicenza, Italy, BTK Italy)	BT SAFE Bone Level—double lead threads with a hexagonal conical connection and integrated platform shifting	Mx: 25 Md: 24
De Angelis et al., 2011 [43]	IPDL	Mc (4 PP)	12	N/A	N/A	91.3	N/A	6 imps were mobile at abutment connection at 3–4 months; 1 imp failed after 3-month loading at 6–7 months after placement	Amoxicillin/clindamycin: 1 h pre-op and 6 days post-op	Endobon® (Biomet 3i), a bovine-derived, deproteinised, osteoconductive hydroxyapatite ceramic	NanoTite™ Tapered Certain® Prevail® titanium alloy (Ti6Al4V) implants (Biomet 3i, Palm Beach, FL, USA) with internal connection. Dual acid etched and then partially covered with nanoscale calcium phosphate crystals. Biomet 3i platform-switched abutments	Mx: 50 Md: 30
Koh et al., 2011 [44]	IPDL	U	12	N/A	N/A	95.5	N/A	1 imp failed with no reason given	Amoxicillin/Azithromycin: pre-op and 7/3 days post-op	Mixture of cortical and cancellous particulates allograft (MinerOss)	Tapered internal implant, BioHorizon, Birmingham, AL	Mx: 21
Prosper et al., 2003 [45]	IPDL	U	3, 6, 9, 12, 24, 36, 48	N/A	N/A	100	N/A	N/A	Augmentin: 6 days post-op	Synthetic hydroxyapatite (Biosite; Vebas, Milan, Italy)	Sandblasted, titanium (Bioactive Covering, Winsix, London, United Kingdom), self-threading cylindric screw, 5.9, 11, or 13 mm	Mx: 75 Md: 36
Urban et al., 2011 [46]	IPDL	Not specified	0.25, 12	N/A	N/A	83.7	N/A	15 imps failed to osseointegrate	Phenoxymethylpenicillin: 5 days pre-op	Autologous bone	Brånemark System, Mk III Groovy, Wide Platform implant (NobelBiocare, Göteborg, Sweden) with an external hex connection, 5.0 mm and a thread spacing of 0.8 mm	Mx: 45 Md: 47
Crespi et al., 2008 [47]	IPL vs. IPDL	U	24	100	N/A	100	N/A	N/A	Amoxicillin: 1 h pre-op and 1 week post-op	Not specified	40 outlink, Sweden & Marina, Pafova implants. 30 implants: 5 mm, 10 implants: 3.75 mm, 13 mm	Mx: 40
Van Nimwegen et al., 2018 [48]	IPR	U	12	N/A	96.7	N/A	N/A	2 imps failed to osseointegrate	Amoxicillin: pre-op and 7 days post-op	Mixture of autogenous bone and Bio-Oss	NobelActive (Nobel Biocare)	Mx: 60

IPR: immediately placed and restored, IPDL: immediately placed and delayed loading, IPL: immediately placed and loaded, DP: delayed placement, RCT: randomised control trial, PS-RCT: prospective randomised control trial, Mc: multicentre, PP: private practice, N/A: not applicable, RBM: resorbable blast media, IIP: immediately placed implants, Mx: maxillary, Md: mandibular.

4. Results

The first electronic search yielded 6042 citations that could be reviewed. After the abstracts were screened, 5674 of these were rejected. Full text assessment was conducted on 368 studies. A total of 193 articles were excluded: 69 studies were excluded on the grounds of mixed results with multi-unit restorations, 55 were rejected as they did not follow-up implant placement to the minimum 1-year mark, 30 were not longitudinal studies, 13 had a sample size less than six, 14 were published prior to 1 January 1999, 10 studies did not do IIP, one study was not published in English, and one study was not on humans (see Table 4).

Furthermore, 17 additional studies were included after manually searching the reference lists of non-excluded studies. An overall total of 192 longitudinal studies were accepted. A further 164 articles were rejected as they were not randomised controlled trials, and 28 articles were accepted; however, two studies were published twice at two different time points during their experiment so their results were combined [21,22,23,24]. A total of 26 randomised controlled trials were included in this study, with an average follow-up time of 24 months (range 12 to 120 months). A diagram detailing the search strategy is shown in the Figure 1.

Subsequently, the bias was assessed using the Cochrane Risk of Bias Tool for randomised controlled trials. A summary is provided in

Table 3. Risk of Bias Analysis. Analysis was done according to the Cochrane Risk of Bias Tool for randomised controlled trials.

Study	Random Sequence Generation	Allocation Concealment	Blinding of Participant & Personnel	Blinding of Outcome Data	Incomplete Outcome Data	Selective Reporting	Other Bias	Overall Quality
Canullo et al., 2009/2017 [21,22]	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk	Unclear risk	Unclear risk
Tallarico et al., 2016/2017 [23,24]	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Cannizzaro et al., 2010 [25]	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk	Unclear risk	Unclear risk
Shibly et al., 2012 [27]	Low risk	Unclear risk	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Blocker et al., 2009 [28]	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Canullo et al., 2010 [29]	Low risk	High risk	Unclear risk	Low risk	High risk	Low risk	Low risk	High risk
De Rouck et al., 2009 [30]	Low risk	Unclear risk	Low risk	Low risk	Low risk	Low risk	Low risk	Unclear risk
Degidi et al., 2014 [31]	Low risk	Unclear risk	Low risk	Low risk	High risk	Low risk	Low risk	High risk
Esposito et al., 2015 [32]	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk	Unclear risk	Unclear risk
Felice et al., 2015 [33]	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk	Unclear risk	Unclear risk
Grandi et al., 2014 [34]	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Migliorati et al., 2015 [35]	Low risk	Unclear risk	Unclear risk	Low risk	Low risk	Low risk	Low risk	Unclear risk
Palatella et al., 2008 [37]	Low risk	Low risk	Low risk	Unclear risk	Low risk	Low risk	Unclear risk	Unclear risk
Pieri et al., 2011 [38]	Low risk	Low risk	Low risk	Unclear risk	Low risk	Low risk	Unclear risk	Unclear risk
Slagter et al., 2015 [39]	Low risk	Unclear risk	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Yoshino et al., 2014 [40]	Low risk	Unclear risk	Unclear risk	Unclear risk	Low risk	Low risk	Low risk	Unclear risk
Zuiderveld et al., 2018 [41]	Low risk	Low risk	Unclear risk	Unclear risk	Low risk	Low risk	Low risk	Unclear risk
Cecchinato et al., 2015 [42]	High risk	Unclear risk	Unclear risk	High risk	High risk	Low risk	Low risk	High risk
Cordaro et al., 2009 [43]	Low risk	Unclear risk	Unclear risk	Unclear risk	Low risk	Low risk	Low risk	High risk
Cucchi et al., 2017 [44]	Low risk	High risk	High risk	Unclear risk	Low risk	Low risk	Low risk	Unclear risk
De Angelis et al., 2011 [45]	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Koh et al., 2011 [46]	Low risk	Unclear risk	Unclear risk	Low risk	High risk	Low risk	Low risk	High risk
Prosper et al., 2003 [47]	Unclear risk	Unclear risk	Low risk	Unclear risk	Low risk	Low risk	Unclear risk	Unclear risk
Crespi et al., 2008 [49]	Unclear risk	Unclear risk	Unclear risk	Unclear risk	Low risk	Low risk	Low risk	Unclear risk
Urban et al., 2011 [48]	Low risk	Unclear risk	Unclear risk	Low risk	Low risk	Low risk	Low risk	Unclear risk
Van Nim-wegen et al., 2018 [50]	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk

.

4.1. Survival Rates

The overall range of survival rates was 40–100%. One study gave survival rates for IPL implants, of 80% [25]. They used zirconia implants, which considered to be rare at that time [26]. Another study has as high as 93.3% survival ate [27]. Fourteen studies gave survival rates for IPR, ranging from 80 to 100% [21,22,25,28,29,30,31,32,33,34,35,36,37,38,39,40,41]. For implants that were IPDL, thirteen studies gave survival rates ranging from 83.7 to 100% [23,24,28,30,32,33,39,42,43,44,45,46,47,48]. Six studies compared immediate implants to conventional DP implants and the survival rates for DP implants in these studies ranged from 97 to 100% [23,24,25,32,33,37,44].

When a study reported a 100% survival rate for immediate implants, regardless of loading protocol (i.e., either IPL, IPR, or IPDL group), all the comparison groups (IPL, IPR, or IPDL) also presented with a 100% survival rate. Eleven RCTs presented with 100% survival rates in immediate implants [21,22,23,24,29,31,34,35,37,39,40,47]. Conversely, three studies reported survival rates less than 90% [25,28,48]. One study in particular reported very a low survival rate of 40% for IPL and 80% for IPR [25].

4.2. Reasons Given for Implant Failure

There were fifteen studies which reported implant failure. Two studies gave no reason for the implant failures [28,46]. The implants failed early in twelve of these studies while four studies reported late implant failure, with three studies presenting both early and late implant failures (refer to

Table 4. Table of Excluded Studies. A total of 189 articles were excluded for the following reasons outlined in the headings [51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,148,149,150,151,152,153,154,155,156,157,158,159,160,161,162,163,164,165,166,167,168,169,170,171,172,173,174,175,176,177,178,179,180,181,182,183,184,185,186,187,188,189,190,191,192,193,194,195,196,197,198,199,200,201,202,203,204,205,206,207,208,209,210,211,212,213,214,215,216,217,218,219,220,221,222,223,224,225,226,227,228,229,230,231,232,233,234,235,236,237,238,239]. A further 162 articles were excluded as they were not randomised controlled trials; these articles are not tabulated above but are included in the references [36,69,77,83,101,107,112,113,118,189,198,210,226,240,241,242,243,244,245,246,247,248,249,250,251,252,253,254,255,256,257,258,259,260,261,262,263,264,265,266,267,268,269,270,271,272,273,274,275,276,277,278,279,280,281,282,283,284,285,286,287,288,289,290,291,292,293,294,295,296,297,298,299,300,301,302,303,304,305,306,307,308,309,310,311,312,313,314,315,316,317,318,319,320,321,322,323,324,325,326,327,328,329,330,331,332,333,334,335,336,337,338,339,340,341,342,343,344,345,346,347,348,349,350,351,352,353,354,355,356,357,358,359,360,361,362,363,364,365,366,367,368,369,370,371,372,373,374,375,376,377,378,379,380,381,382,383,384,385,386,387,388].

Follow-Up	Multiple-Units	Sample Size	Year of Publication	Not a Clinical Study	Non-Immediate Implants	Not in English	Animal Study
Amato et al., 2018 [51]	Al Nashar and Yakoob 2015 [52]	Chu et al., 2012 [53]	Becker et al., 1998 [54]	Lang et al., 2012 [10]	Boardman et al., 2016 [56]	Kohal et al., 2002 [57]	De Sanctis et al., 2009 [58]
Assaf et al., 2017 [59]	Alves et al., 2010 [60]	Cornelini et al., 2000, [61]	Becker et al., 1992 [62]	Chen et al., 2014 [12]	Buser et al., 2013 [64]
Basa et al., 2004 [65]	Anitua et al., 2016 [66]	De Molon et al., 2015 [67]	Garber et al., 1995 [68]	Aires and Berger 2002 [55]	Casap et al., 2007 [70]
Bell et al., 2014 [71]	Blus et al., 2006 [72]	Harvey 2007 [73]	Gelb 1993 [74]	Becker 2006 [63]	Eghbali et al., 2012 [76]
Botticelli et al., 2004 [77]	Eghbali et al., 2012 [76]	Park et al., 2010 [79]	Gomez-Roman et al. 1997, [80]	Becker et al., 2011 [69]	Le et al., 2014 [81]
Caiazzo et al., 2013 [82]	Bogaerde et al., 2010 [78]	Paul 2007 [84]	Hammerle et al., 1998 [85]	Bruno et al., 2012 [75]	Proussaefs et al., 2002 [87]
Calvo Guirado et al., 2007 [88]	Cosyn et al., 2013 [83]	Peñarrocha et al., 2006 [90]	Lang et al., 1994 [91]	Chang et al., 2009 [86]	Ryser et al., 2005 [93]
Chen et al. 2009, [94]	Covani et al., 2003 [89]	Rebele 2013 [96]	Rosenquist and Grenthe 1996 [97]	Chen et al., 2009 [92]	Sarnowski et al., 2012 [99]
Chu et al., 2015 [100]	Covani et al., 2004 [95]	Ross et al., 2013 [102]	Schwartz-Arad 1997 [103]	Daif et al., 2013 [98]	Schropp et al., 2003 [105]
Chu et al., 2018 [106]	Crespi et al., 2007 [101]	Schiroli 2003 [108]	Schwartz-Arad 1998 [109]	Enrique-Sacristan et al., 2011 [104]	Schropp et al., 2005 [111]
Covani et al., 2004 [112]	Crespi et al., 2009 [107]	Trimpou et al., 2010 [114]	Simion et al., 1992 [115]	Froum et al., 2007 [110]
Covani et al., 2008 [117]	Crespi et al., 2010 [113]	Turkyilmaz et al., 2009 [119]	Tritten et al., 1995 [120]	Fugazzotto and Hains 2013 [116]
Di Girolamo et al., 2016 [122]	Capelli et al., 2010 [118]		Werbitt and Goldberg 1992 [124]	Fugazzotto et al., 2012 [121]
El Chaar et al., 2011 [126]	Crespi et al., 2014 [123]		Wilson 1992 [128]	Gluckman et al., 2018 [125]
Evian et al., 2004 [130]	Crespi et al., 2018 [127]		Wöhrle 1998 [132]	Greenstein and Cavallaro 2014 [129]
Felice et al., 2011 [134]	Danza et al., 2009 [131]			Holst et al., 2007 [133]
Felice et al., 2016 [137]	Davarpanah et al., 2005 [135]			Kan et al., 2000 [136]
Fernandes Diaz et al., 2012 [140]	Degidi et al., 2007 [138]			Kan et al., 2001 [139]
Ferrus et al., 2010 [143]	Degidi et al., 2005 [141]			Kan et al., 2005 [142]
Granić et al., 2015 [146]	Del Fabbro et al., 2009 [144]			Kan et al., 2018 [145]
Groenendij et al., 2017 [149]	Deng et al., 2010 [147]			Kher et al., 2015 [148]
Grunder 2011 [151]	Erakat et al., 2008 [152]			Koh et al., 2010 [150]
Hossain et al., 2017 [153]	Finne et al., 2007 [154]			Lemongello 2007 [155]
Huynh-Ba et al., 2019 [156]	Fugazzotto 2002 [157]			Levine et al., 2018 [158]
Jofre et al., 2012 [159]	Fugazzotto 2008 [160]			Meltzer 2009 [161]
Kamperos et al., 2016 [162]	Gokcen-Rohlig et al., 2010 [163]			Palti 2004 [164]
Kolinski et al., 2014 [165]	Gomez-Roman et al., 2001 [166]			Ramsey 2007 [167]
Lang et al., 2007 [168]	Grunder et al., 1999 [169]			Saadoun 2002 [170]
Lee et al., 2014 [171]	Han et al., 2016 [172]			Waki 2016 [173]
Levin and Chu 2018 [174]	Hayacibara et al., 2013 [175]			Weigl et al., 2016 [176]
Lops et al., 2008 [177]	Heineman et al., 2013 [178]			Yan et al., 2016 [179]
Malo et al., 2000 [180]	Herinemann et al., 2009 [181]
Matarasso et al., 2009 [182]	Horwitz et al., 2007 [183]
Miyamoto 2011 [184]	Jo et al., 2001 [185]
Nemcovsky et al., 1999 [186]	Khorsand et al., 2016 [187]
Nemcovsky et al., 2000 [188]	Laviv et al., 2010 [189]
Nemcovsky et al., 2002 [190]	Malchiodi et al., 2010 [191]
Parel and Schow 2005 [192]	Malchiodi et al., 2011 [193]
Peron et al., 2016 [194]	Malo et al., 2003 [195]
Pirker and Kocher 2009 [196]	Mankoo 2008 [197]
Redemagni et al., 2009 [198]	McAllister et al., 2012 [199]
Rieder et al., 2016 [200]	Meltzer 2012 [201]
Runcharassaeng et al., 2012 [202]	Mura 2012 [203]
Rungcharassaeng et al., 2012 [202]	Noelken et al., 2014 [204]
Saito et al., 2016 [205]	Noelken et al., 2014 [206]
Sanz et al., 2010 [207]	Noelken et al., 2016 [208]
Sarnachiaro et al., 2016 [209]	Noelken et al., 2018 [210]
Scarano 2017 [211]	Ormanier and Palti 2008 [212]
Somanthan et al., 2007 [213]	Ormanier et al., 2012 [214]
Tomasi et al., 2010 [215]	Paolantonio et al., 2001 [216]
Van Kesteren et al., 2010 [217]	Peñarrocha-Diago et al., 2012 [218]
Vanderweghe et al., 2013 [219]	Peñarrocha-Oltra et al., 2012 [220]
Vidigal et al., 2017 [221]	Perry and Lenchewski 2004 [222]
West and Oates 2007 [223]	Polizzi et al., 2000 [224]
Younis et al., 2009 [225]	Siebers et al., 2010 [226]
	Siebert et al., 2015 [227]
	Simsek and Simsek 2003 [228]
	Stefanski et al., 2017 [229]
	Tsai et al., 2000 [230]
	Van Steenberghe et al., 2000 [231]
	Vanden Bogaerde et al., 2005 [232]
	Vidal et al., 2010 [233]
	Villa and Rangert 2007 [234]
	Wagenberg and Froum 2006 [235]
	Wagenberg et al., 2013 [236]
	Wagenberg et al., 2015 [237]
	Wilson et al., 2003, [238]
	Wychowanski et al., 2017 [239]

). Nine studies gave lack of osseointegration as the reason for implant failure [7,25,30,36,41,42,44,45,48]. Other reasons for the implant failure included infection [27], abscess [38], mobility after loading in the IPL group [25], a patient who met the exclusion criteria but was included inadvertently [25], and an iatrogenic mistake where the clinician did not provide enough relief between an implant and the provisional denture [43].

4.3. Patient Selection Criteria

A list of the patient selection criteria in each study is summarised in

Table 5. Inclusion and exclusion criteria of included studies.

Study	Inclusion Criteria	Exclusion Criteria
Block et al., 2009, [28]	Present for recalls and maintenance cleaning. Single rooted maxillary central or lateral incisor, canine, or premolar, with no signs of acute infection (purulent exudate, erythema, pain, and swelling). Intact first molar occlusion to control occlusal forces on the implant restoration. Intact bony socket within 3 mm of the gingival margin of the planned restoration. Adequate space for satisfactory restoration. No active periodontal disease or exhibited controllable periodontal disease such that their teeth were clinically nonmobile and had probing depths less than 3 mm. Crown–root ratio of at least 1:2. 2 mm of attached or keratinized gingiva. Crestal bone sufficient for 4 mm diameter implant for the central incisor, canine, and premolar sites, or a 3.25 mm diameter implant.	ASA III or IV. Postmenopausal women with known osteoporosis. Alcohol abuse was excluded. No uncontrolled diabetes (any type), existing malignancy, and were not receiving any therapy that suppresses their immune system.
Cannizzaro et al., 2010, [25]	Requires one single implant. Residual bone height of at least 10 mm and a thickness of at least 5 mm. Informed consent.	General contraindications to implant surgery. No opposite occluding dentition in the area. Acute infection. Immunosuppression or immunodepression. Active periodontitis. Poor OH. Irradiation in the head or neck area. Bruxism. Treatment or past treatment with intra-venous amino bisphosphonates. Uncontrolled diabetes. Pregnant or lactating. Substance abuse. Psychiatric disorders or unrealistic expectations. Participation in other clinical trials. Unable to be followed for at least 1 year. Requiring the use of a membrane at implant placement. Subjectively evaluated sites as soft bone quality. Implants placed with an insertion torque < 35 Ncm.
Canullo et al., 2009/2017, [21,22]	Single tooth scheduled for extraction. Maxillary tooth from right second bicuspid to left one. Well-preserved alveolar ridge after extraction. General good health.	Acute infection. FMPS and a FMBS > 25%. Interproximal space narrower than 9 mm or with interproximal and buccal bone defects. Smoking >10 cigarettes per day. Uncontrolled diabetes (glycaemic level > 110 mg/L and HbA1c > 6%). Pregnant or lactating.
Canullo et al., 2010, [29]	≥18 years. Requires a single implant in premolar areas of the maxilla. FMPS and FMBS < 25%. Opposing natural teeth. Adjacent teeth. Intact alveolar bone walls. At least 4 mm of bone beyond the root apex.	Chronic systemic diseases. Smoking >10 cigarettes per day. Pregnant or lactating females. Acute infection at the sites. Interproximal space narrower than 9 mm. Interproximal or buccal bone defects.
Cecchinato et al., 2015, [42]	≥18 years of age subjects in need of one or more implants replacing teeth to be removed from 15 to 25. Presence of at least 20 teeth with expected functional occlusion. Intact extraction socket suitable for both cylindrical and conical/cylindrical implants. A marginal border of the facial bone crest that deviated 2 mm from normal location. Potential facial fenestration at least 3 mm apical of the marginal bone crest.	Untreated rampant caries and uncontrolled periodontal disease. Absence of adjacent (mesial and/or distal) natural tooth root. Uncontrolled diabetes or any other systemic or local disease. Systemic corticosteroids. Unable to return for follow-up. Unlikely to be able to comply. Bone alterations after immediate implant installation. Cigarette consumption in excess of 10 cigarettes or equivalent/day.
Cordaro et al., 2009, [43]	Type 1 procedure to replace maxillary incisors, canines and premolars or mandibular canines or premolars. 18–70 years old.	Systemic diseases. Uncontrolled periodontitis. Inadequate oral hygiene. Heavy smoking (4–10 cigarettes/day). Adjacent implants. If, at the moment of placement, the horizontal distance between the implant and the bony walls of the socket was 42 mm the patient should not be evaluated for the study purposes.
Crespi et al., 2008, [49]	4 bony walls of the alveolus. At least 4 mm of bone beyond the root apex. Adjacent teeth. Good health. No chronic systemic disease. Informed consent. Immediate loading of the implants was performed with an implant stability quotient > 60 and implant insertion torque > 25 Ncm.	Dehiscence or fenestration of the residual bony walls. Uncontrolled diabetes. Coagulation disorders. Acute infection around the alveolar bone at the surgical site. Heavy smoking (more than 10 cigarettes per day). Alcohol or drug abuse. Bruxism.
Cucchi et al., 2017, [44]	One single immediate post-extractive implant in the posterior maxilla and mandible (only premolar and molar regions). Adequate bone volume to place an implant at least 3.7 mm in diameter and 10 mm in length, without bone augmentation procedures. Natural occluding dentition. Comprehension, acceptance, and full compliance for the treatment and follow-up.	Available bone length < 10 mm and bone width < 4.5 mm. Untreated and/or active periodontitis. FMPI > 20%; FMBI > 20%. Heavy smoking habit (>20 cigarettes/day). General contraindication to implant surgery. Uncontrolled systemic diseases. Immunosuppression. HIV/HCV/HBV infection. Chemotherapy and/or irradiation in the head and neck area. Treatment with amino bisphosphonates. Pregnancy or nursing. Inability to complete follow up.
De Angelis et al., 2011, [45]	≥18 years. Single-tooth replacement in upper arch from premolar to central incisor. Good oral hygiene. Tooth to be replaced should have been in place at the time of study enrolment. Alveolar bone walls intact. Adjacent teeth in place.	General contraindications to implant surgery. Immunosuppressed or immunocompromised patients. Irradiation in the head or neck area. Uncontrolled diabetes. Pregnant or lactating. Untreated periodontitis. Poor oral hygiene. Substance abuse. Psychiatric disorders or unrealistic expectations. Acute infection (abscess) in the site intended for imp placement. Necessity to lift the maxillary sinus epithelium. Unable to follow-up post loading. IV amino bisphosphonates. Participation in other clinical trials interfering with the present protocol. Missing buccal bone sufficient to compromise the aesthetic outcome.
De Rouck et al., 2009, [30]	Good OH. Gingival harmony. Normal to thick biotype. Apical bone ≥ 5 mm	Systemic disease. Smoking ≥ 10 cigarettes/day. Bruxism. Lack of posterior support. Active periodontitis. Loss of labial bone.
Degidi et al., 2014, [31]	≥18 years of age. Single compromised tooth in canine to canine maxillary anterior sector.	Active infection. Systemic disease that could compromise osseointegration. Radiation therapy in the craniofacial region within the previous 12 months. Smoking > 10 cigarettes per day. Pregnancy or lactation. Bruxism. Unsuitable quantity of bone in the surgery site or need of bone augmentation procedures prior to implant placement. Implant insertion torque < 25 Ncm. ISQ < 60. Dehiscence, fenestration, or fracture.
Esposito et al., 2015, [32]	One single immediate post-extractive implant in the maxilla from second to second premolar. Adjacent teeth. ≥18 years old. Signed an informed consent form. Sufficient bone to allow the placement of a single implant at least 7 mm long with a 4 mm diameter.	General contraindications to implant surgery. Immunosuppressed or immunocompromised. Irradiation in the head or neck area. Uncontrolled diabetes. Pregnant or lactating. Untreated periodontitis. Poor oral hygiene. Substance abuse. Psychiatric disorders. Acute infection. Necessity to lift the maxillary sinus epithelium. Unable to attend recalls. Intravenous amino bisphosphonates. Participation in other clinical trials interfering with present protocol. More than 4 mm in height of the buccal wall was missing after tooth extraction.
Felice et al., 2015, [33]	One single immediate post-extractive implant in the maxilla from second to second premolar. Adjacent teeth. ≥18 years old. Signed an informed consent form. Sufficient bone to allow the placement of a single implant at least 8 mm long with a minimal diameter of 3.8 mm. For patients who required multiple edentulous areas to be restored, the operator was free to select one implant site to be included in the trial at the screening visit.	General contraindications to implant surgery. Immunosuppressed or immunocompromised. Irradiation in the head or neck area. Uncontrolled diabetes. Pregnancy or lactation. Untreated periodontitis. Poor oral hygiene and motivation. Addiction to alcohol or drugs. Psychiatric disorders. Unrealistic expectations. Acute infection (abscess). Necessity to lift the maxillary sinus epithelium. Unable to commit to follow-up. IV amino bisphosphonates. Lack of one or both adjacent natural teeth. >4 mm of buccal wall missing (in terms of height), assessed using the highest peak of the palatal wall as a reference point. Participation in other studies which interfere with present protocol.
Grandi et al., 2014, [34]	≥18 years of age. Single immediate post-extractive implant from 15 to 25 with adjacent teeth. Sufficient bone to allow the placement of an implant at least 11.5 mm long with a 3.7 mm diameter. Maximum plaque index score of 13 less than or equal to 2.	Dehiscence or lack of buccal bone plate after tooth extraction. General contraindications to implant surgery. Irradiation in the head and neck area. Immunosuppressed or immunocompromised patientsTreated or under treatment with IV bisphosphonates. Uncontrolled diabetes. Substance abuse. Heavy smoking (20 cigarettes daily). Lack of opposing occluding dentition.
Koh et al., 2011, [46]	>18 years of age. Systemically healthy. Tooth in the maxillary premolar or anterior region requiring extraction. Stable occlusion, adjacent and opposing teeth. Healthy periodontium.	Unstable systemic disease precluding surgical procedures. Compromised healing conditions. Bone disorders. Pregnant. Alcoholism or recreational drug abuse. Smoking > 10 cigarettes per day, long term (>2 weeks). Anti-inflammatories. Steroids. Bisphosphonates in the past 3 months. O’Leary plaque score > 20%. Parafunctional habits. Active dental disease. Anatomic limitations.
Migliorati et al., 2013, [35]	>21 years. Absence of periodontal disease. Adequate bone to achieve implant primary stability. KM width of at least 2 mm. Soft tissue level on the same level to the contralateral tooth. Single-tooth replacement in the anterior maxilla (from first bicuspid to first bicuspid).	Systemic diseases that could alter the tissue integration of dental implants. Pregnancy. Smoking > 10 cigarettes per day.
Palatella et al., 2008, [37]	≥18 years. Single-tooth replacement in maxillary arch from premolar to central incisor. Good oral hygiene. Tooth to be replaced present at the time of enrolment, Alveolar bone walls intact after the extraction. Adjacent teeth were in place.	Uncontrolled diabetes. Coagulation impairments. Acute infections and/or suppuration at the surgical site. Bruxers.
Pieri et al., 2011, [38]	FMPS and FMBS < 25%. Four intact bony walls. ≥4 mm bone beyond apex. ≥3 mm KM. Presence of adjacent/opposing teeth.	Tobacco use (>20 cigarettes/day). History of radiotherapy in the head and neck region. Severe bleeding disorder. Diabetes mellitus. Pregnancy or lactation. Alcohol or drug abuse. Psychiatric problems. Bruxism or clenching. Untreated periodontitis. Acute infection and/or suppuration.
Prosper et al., 2003, [47]	21–75 years. Compliance with home oral hygiene. Extraction because of caries, dental fracture, periodontitis, or endodontic treatment failure. Sufficiently wide, fresh extraction socket such that after 5.9 mm-diameter implant there would still be a residual bone defect. Good occlusion.	Criterion for exclusion was the presence of any dysmetabolic, chronic, and/or infectious disease.
Shibly et al., 2012, [27]	Maintenance periodontal recall after receiving active periodontal treatment because of a past history of periodontal disease. Single implant to replace a “hopeless” tooth. ESOP were included in this surgical protocol. GBR procedures were indicated to treat all ESOP defects.	Compromised general health conditions. Chemotherapy for the treatment of cancer. Antimetabolic therapy (e.g., methotrexate) for the treatment of arthritis. Uncontrolled diabetes. Severely impaired cardiovascular function. Immunodeficiency. Kidney or liver disease. Bruxism.
Slagter et al., 2015, [39]	≥18 years old. Failing single tooth in maxillary aesthetic zone (up to first premolar) Adequate OH	Buccal socket wall with bony defect ≥5 mm in a vertical direction.
Tallarico et al., 2016/2017, [23,24]	One implant-supported single restoration to replace a failed tooth in the molar region of both jaws. Less than 5 mm between the root apex and the inferior alveolar nerve or maxillary sinus. ≥18 years old. Signed informed consent form. Fresh extraction sockets had to have intact buccal walls after extraction.	General contraindications to oral surgery (such as stroke, recent cardiac infarction, severe bleeding disorder, uncontrolled diabetes or cancer). Heavy smokers (≥11 cigarettes/day). Addiction to alcohol or drugs. Acute and chronic infections in the site intended for implant placement. Full mouth bleeding and full mouth plaque index higher than 25%. Pregnancy or nursing. Psychiatric therapy. Intravenous amino bisphosphonates. Radiotherapy of the oral and maxillofacial region within the last 5 years. Absence of opposing teeth. Severe clenching or bruxism. Unable to commit to the scheduled follow-up.
Urban et al., 2011, [48]	>18 years of age. Classified as ASA class 1—a normal healthy patient, and class 2—a patient with mild systemic disease (e.g., mild hypertension). Molar tooth. Adequate bone for placing at least a 10 mm long implant.	Systemic diseases affecting bone turnover and pregnant or lactating women.
Van Nimwegen et al., 2018, [50]	≥18 years of age. Incisor, canine, or first bicuspid in the maxilla. Adjacent and opposing natural teeth. Adequate oral hygiene. Absence of active and uncontrolled periodontal disease. Sufficient mesial–distal and interocclusal space for placement of the implant and definitive restoration. Sufficient interocclusal space to design a non-occluding provisional restoration. An intact facial bone wall is present on the preoperative CBCT.	ASA score ≥ III. Periodontal disease. Smoking. Radiotherapy to the head and neck region. Pregnancy. Post-extraction bony defect and a distance that exceeded 5 mm.
Yoshino et al., 2014, [40]	≥18 years or older. Good OH. Single failing maxillary tooth in the aesthetic zone (between and including the first premolars). Adjacent and opposing natural dentition. No active infection. Sufficient bone volume to accommodate placement of a single implant with minimum dimensions of 3.3 × 12.0 mm.	A history of smoking or head and neck radiation treatment. Bruxism and/or parafunction. Lack of stable posterior occlusion. In whom primary implant stability could not be achieved
Zuiderveld et al., 2018, [41]	≥18 years of age. Modified plaque and sulcus bleeding index ≤1. Diastema width of ≥6 mm and sufficient inter-occlusal space for a non-occluding provisional restoration. No medical and general contraindications for the surgical procedure. No active and uncontrolled periodontal disease. Buccal socket wall had a bony defect of <5 mm in a vertical direction.	Smokers. Received head neck radiation. Pregnant

ASA: American Society of Anesthesiologists, FMPS: full mouth plaque score, FMBS: full mouth bleeding score, OH: Oral hygiene, FMPI: full mouth plaque index, FMBI: full mouth bleeding index, HCV: hepatitis C virus, HBV: hepatitis B virus, HIV: human immunodeficiency virus, CBCT: cone beam computed tomography, IV: intravenous, ESOP: extraction sockets with an open defect, KM: keratinised labial mucosa, GBR: guided bone regeneration.

. Most studies required their patients to be systemically healthy (n = 24), with no acute infection, either periapical or periodontal, in the area of implant placement (n = 22) and having an intact tooth socket or sufficient buccal bone after extraction (n = 22). These studies are listed in

Table 6. List of articles that specified the above patient inclusion criteria.

Systemically Healthy	No Acute Periodontal/Peri-Apical Infection in Area	Intact Tooth Socket or Sufficient Buccal Bone
Block et al., 2009, [28]	Block et al., 2009, [28]	Block et al., 2009, [28]
Cannizzarro et al., 2010, [25]	Cannizzarro et al., 2010, [25]	Cannizzarro et al., 2010, [25]
Canullo et al., 2009/2017, [21,22]	Canullo et al., 2009/2017, [21,22]	Canullo et al., 2009/2017, [21,22]
Canullo et al., 2010, [29]	Canullo et al., 2010, [29]	Canullo et al., 2010, [29]
Cecchinato et al., 2015, [42]	Cecchinato et al., 2015, [42]	Cordaro et al., 2009, [43]
Cordaro et al., 2009, [43]	Cordaro et al., 2009, [43]	Crespi et al., 2008, [49]
Crespi et al., 2008, [49]	Crespi et al., 2008, [49]	Cucchi et al., 2017, [44]
Cucchi et al., 2017, [44]	Cucchi et al., 2017, [44]	De Angelis et al., 2011, [45]
De Angelis et al., 2011, [45]	De Angelis et al., 2011, [45]	De Rouck et al., 2009, [30]
De Rouck et al., 2009, [30]	De Rouck et al., 2009, [30]	Degidi et al., 2014, [31]
Degidi et al., 2014, [31]	Degidi et al., 2014, [31]	Esposito et al., 2015, [32]
Esposito et al., 2015, [32]	Esposito et al., 2015, [32]	Felice et al., 2015, [33]
Felice et al., 2015, [33]	Felice et al., 2015, [33]	Grandi et al., 2014, [34]
Grandi et al., 2014, [34]	Koh et al., 2011, [46]	Migliorati et al., 2015, [35]
Koh et al., 2011, [46]	Migliorati et al., 2015, [35]	Pallatella et al., 2008, [37]
Migliorati et al., 2015, [35]	Pallatella et al., 2008, [37]	Pieri et al., 2011, [38]
Pallatella et al., 2008, [37]	Pieri et al., 2011, [38]	Slagter et al., 2015, [39]
Pieri et al., 2011, [38]	Shibly et al., 2012, [27]	Tallarico et al., 2016/2017, [23,24]
Prosper et al., 2003, [47]	Tallarico et al., 2016/2017, [23,24]	Urban et al., 2012, [48]
Shibly et al., 2012, [27]	Van Nimwegen et al., 2018, [50]	Van Nimwegen et al., 2018, [50]
Tallarico et al., 2016/2017, [23,24]	Yoshino et al., 2014, [40]	Yoshino et al., 2014, [40]
Urban et al., 2012, [48]	Zuiderveld et al., 2018, [41]	Zuiderveld et al., 2018, [41]
Van Nimwegen et al., 2018, [50]
Zuiderveld et al., 2018, [41]

.

Ten studies did not specify inclusion or exclusion of smokers and ten studies included smokers of ≤10 cigarettes a day. Three studies that did not specify smoking and six studies that included smoking ≤10 cigarettes a day achieved 100% survival rates. Three studies excluded smoking completely and three studies included smokers of ≤20 cigarettes a day, and all achieved survival rates >95%. Of the eleven studies achieving 100% survival rates across all categories, most included patients who smoked ≤10 cigarettes a day. Smoking inclusion is tabulated in

Table 7. Studies that included or excluded smokers.

	Excluded Smokers	Included Smokers of ≤10 Cigarettes/Day	Included Smokers of >20 Cigarettes a Day	Did Not Exclude or Include Smokers
	Van Nimwegen et al., 2018, [50]	Canullo et al., 2009/2017, [21,22] *	Cucchi et al., 2017, [44]	Block et al., 2009, [28] #
	Yoshino et al., 2014, [40] *	Canullo et al., 2010, [29] *	Grandi et al., 2014, [34] *	Cannizzaro et al., 2010, [25] #
	Zuiderveld et al., 2018, [41]	Cecchinato et al., 2015, [42]	Pieri et al., 2011, [38]	Cordaro et al., 2009, [43]
		Crespi et al., 2008, [49] *		De Angelis et al., 2011, [45]
		De Rouck et al., 2009, [30]		Esposito et al., 2015, [32]
		Degidi et al., 2014, [31] *		Felice et al., 2015, [33]
		Koh et al., 2011, [46]		Palattella et al., 2008, [37] *
		Migliorati et al., 2015, [35] *		Prosper et al., 2003, [47] *
		Tallarico et al., 2016/2017, [23,24] *		Shibly et al., 2012, [27]
		Urban et al., 2012, [48] #		Slagter et al., 2015, [39] *
Survival rate ranges	96.7–100%	83.7–100%	95.5–100%	40–100%

Asterisk (*) indicates studies with 100% survival rates for immediate single implants. Hashtag (#) indicates studies with survival rates of less than 90% for immediate single implants.

.

4.4. Loading Protocol

Three studies investigated the effect of IPL implants. Four out of 51 IPL implants failed from the three studies. Only one out of these three studies reported a survival rate of <90%. One of these studies compared IPL and IPDL with survival rates of 96.6% (1 out of 26 implants failed) and 93.3% (2 out of 29 implants failed), respectively [27]. Even though the survival rate for the IPL implants was slightly higher, they did not find that the difference was significant.

One study by Cucchi et al. [44] loaded the implants early where definitive crowns were placed one week after implant placement. Two implants were lost out of the 49 implants that were placed in fresh extraction sockets (95.5% survival rate).

The remaining studies placed definitive restorations 3–6 months after placements (IPR or IPDL implants). All 11 studies that achieved a 100% survival rate had at least one experimental group using IPR or IPDL implants. Twelve studies reported survival rates between 91.3 and 98.9%, and three studies reported survival rates between 80 and 84.6% for IPR or IPDL implants. These are tabulated in

Table 8. Studies divided based on loading protocols used for the implants.

	IPL Implants	IPR Implants	IPDL Implants
	Cannizzaro et al., 2010, [25] #	Block et al., 2009, [28] #	Block et al., 2009, [28] #,†
	Crespi et al., 2008, [49] *	Cannizzaro et al., 2010, [25] #	Cecchinato et al., 2015, [42] †
	Shibly et al., 2012, [27] †	Canullo et al., 2009/2017, [21,22] *	Cordaro et al., 2009, [43] †
		Canullo et al., 2010, [29] *	Crespi et al., 2008, [49] *
		De Rouck et al., 2009, [30] †	Cucchi et al., 2017, [44] †
		Degidi et al., 2014, [31] *	De Angelis et al., 2011, [45] †
		Grandi et al., 2014, [34] *	De Rouck et al., 2009, [30]
		Migliorati et al., 2013, [35] *	Koh et al., 2011, [46] †
		Van Nimwegen et al., 2018, [50] †	Prosper et al., 2003, [47] *
		Palatella et al., 2008, [37] *	Shibly et al., 2012, [27] †
		Pieri et al., 2011, [38] †	Slagter et al., 2015, [39] *
		Slagter et al., 2015, [39] *	Tallarico et al., 2016/2017, [23,24] *
		Yoshino et al., 2014, [40] *	Urban et al., 2011, [48] #
		Zuiderveld et al., 2018, [41] †
Survival rate ranges	40–100%	80–100%

Asterisk (*) indicates studies with 100% survival rates in at least one experimental group. Obelisk (†) indicates studies reporting survival rates between 91.3 and 98.9% in at least one experimental group. Hashtag (#) indicates studies with survival rates between 80 and 84.6% in the experimental group.

.

4.5. Antibiotic Therapy

Most studies used amoxicillin (n = 21). Among them, six studies used amoxicillin with clavulanic acid, six studies allowed substitution with clindamycin, and two studies allowed substitution of amoxicillin with azithromycin [46] or clarithromycin [34] if the patients were allergic to penicillin. All but one of these studies yielded a survival rate greater than 90% [25], with eleven of these studies yielding 100% survival across all categories of placement and loading. One study did not specify which antibiotic they used, but the study yielded 100% survival [40]. Two studies used phenoxymethylpenicillin [48] and cephalosporin [28], respectively, and both studies yielded survival rates below 90%. Two other studies did not use antibiotics, but yielded survival rates of 96.6% and 98.9%. The studies are listed in

Table 9. Studies divided based on the type of antibiotics used.

Amoxicillin	Amoxicillin with Clavulanic Acid	Antibiotics Used Not Specified	Other Antibiotics Used	Did Not Use Antibiotics
Cannizzaro et al., 2010, [25] #,‡	Canullo et al., 2010, [29] *	Yoshino et al., 2014, [40] *	Block et al., 2009, [28] #,Δ	Cecchinato et al., 2015, [42] †
Crespi et al., 2008, [49] *	Canullo et al., 2009/2017, [21,22] *		Urban et al., 2012, [48] #,¶	Cordaro et al., 2009, [43] †
Cucchi et al., 2017, [44]	Grandi et al., 2014, [34] *,‖
De Angelis et al., 2011, [45] ‡	Palattella et al., 2008, [37] *
De Rouck et al., 2009, [30]	Pieri et al., 2011, [38]
Degidi et al., 2014, [31] *	Prosper et al., 2003, [47] *
Esposito et al., 2015, [32] ‡
Felice et al., 2015, [33] ‡
Koh et al., 2011, [46] §
Migliorati et al., 2013, [35] *,‡
Shibly et al., 2012, [27]
Slagter et al., 2015, [39] *
Tallarico et al., 2016/2017, [23,24] *
Van Nimwegen et al., 2018, [50]
Zuiderveld et al., 2018, [41] ‡

(*) indicates studies with 100% survival rates in at least one experimental group. (†) indicates studies reporting survival rates between 96.6 and 98.9%. (#) indicates studies with survival rates below 90% in at least one experimental group. (‡) indicates studies that used amoxicilin but allowed substitution with clindamycin. (§) indicates studies that used amoxicillin but allowed substitution with azithromycin. (‖) indicates studies that used amoxicillin but allowed substitution with clarithromycin. (¶) indicates study that used phenoxymethylpenicillin. (Δ) indicates study that used cephalosporin.

.

Twelve studies used antibiotics both pre-operatively and post-operatively. Of these studies, four had 100% survival rates and the rest had survival rates greater than 90%. Four studies only used antibiotics post-operatively, three of which had survival rates of 100% and one with a survival rate less than 90%. Five studies only used antibiotics pre-operatively, four of which had 100% survival rates and one had a survival rate lower than 90%. Three studies only used post-operative antibiotics if a graft was used, and survival rates ranged from 40 to 95.9%. The studies are listed in

Table 10. Studies divided based on antibiotics regimen.

	Used Pre-Operative Antibiotics Only	Used Post-Operative Antibiotics Only	Used Both Pre- and Post-Operative Antibiotics	Only Used Post-Operative Antibiotics When Graft Was Used
	Canullo et al., 2010, [29] *	Block et al., 2009, [28] #	Canullo et al., 2009/2017, [21,22] *	Cannizarro et al., 2010, [25] #
	Migliorati et al., 2015, [35] *	Palattella et al., 2009, [37] *	Crespi et al., 2008, [49] *	Esposito et al., 2015, [32]
	Slagter et al., 2015, [39] *	Prosper et al., 2003, [47] *	Cucchi et al., 2017, [44]	Felice et al., 2015, [33]
	Tallarico et al., 2016/2017, [23,24] *	Yoshino et al., 2014, [40] *	De Angelis et al., 2011, [45]
	Urban et al., 2012, [48] #		De Rouck et al., 2008, [30]
			Degidi et al., 2014, [31] *
			Grandi et al., 2014, [34] *
			Koh et al., 2011, [46]
			Pieri et al., 2011, [38]
			Shibly et al., 2012, [27]
			Van Nimwegen et al., 2018, [50]
			Zuiderveld et al., 2018, [41]
Survival rate ranges	87.3–100%	84.6–100%	91.3–100%	40–95.9%

Asterisk (*) indicates studies with 100% survival rates in at least one experimental group. Hashtag (#) indicates studies with survival rates below 90% in at least one experimental group.

.

4.6. Setting

Twelve studies were conducted in a private practice (PP), of which nine were multicentre (Mc) studies, eleven studies were conducted in a university setting (U), and three studies did not specify the location of the study (NS).

Of the studies that achieved 100% survival rates for immediate implants, five were conducted in private practices, four were in universities, and one with an unspecified setting. Of the studies with a survival rate of less than 90% for immediate implants, one was conducted in a private practice [25] and had survival rates of 40% for IPL and 80% for IPR implants. The other two did not specify the setting [28,48]. The studies are listed in

Table 11. Studies divided based on the setting in which the study was conducted.

	Private Practice	University	Non-Specified
	Cannizarro et al., 2010, [25] #	Crespi et al., 2008, [49] *	Block et al., 2009, [28] #
	Canullo et al., 2010, [29] *,^	De Rouck et al., 2008, [30]	Migliorati et al., 2015, [35] *
	Canullo et al., 2009/2017, [21,22] *,^	Koh et al., 2011, [46]	Urban et al., 2012, [48] #
	Cecchinato et al., 2015, [42] ^	Palattella et al., 2008, [37] *
	Cordaro et al., 2009, [43]	Pieri et al., 2011, [38]
	Cucchi et al., 2017, [44] ^	Prosper et al., 2003, [47] *
	De Angelis et al., 2011, [45] ^	Shibly et al., 2012, [27]
	Degidi et al., 2014, [31] *	Slagter et al., 2015, [39] *
	Esposito et al., 2015, [32]	Van Nimwegen et al., 2018, [50]
	Felice et al., 2015, [33]	Yoshino et al., 2014, [40] *
	Grandi et al., 2014, [34] *,^	Zuiderveld et al., 2018, [41]
	Tallarico et al., 2016/2017, [23,24] *
Survival rate ranges	40–100%	92–100%	84.6–100%

Asterisk (*) indicates studies with 100% survival rates in at least one experimental group. Hashtag (#) indicates studies with survival rates below 90% in at least one experimental group. (^) indicates multicentre studies.

.

4.7. Grafting Materials

Five studies did not use bone grafts, all of which had survival rates from 95 to 100%. Nine studies used xenografts, seven of which were bovine. Bio-Oss^® (Geistlich Pharma AG, Wolhusen, Switzerland) was the graft of choice in four of those studies [30,32,34,40]. Canullo et al., 2009/2016, and Migliorati et al., 2013, used Bio-oss^® Collagen (Geistlich-Pharma AG, Wolhusen, Switzerland) and Bio-Oss^® Collagen (Geistlich PharmaNorth America, Inc., Princeton, NJ, USA), respectively [21,22,35]. Endobon^® (Biomet 3i) is a bovine-derived osteoconductive hydroxyapatite used by De Angelis et al., 2011, and Felice et al., 2015, used an algae-derived bone substitute (FRIOS^® Algipore^®, Dentsply, Friadent, Mannheim, Germany) [33,45]. Lastly, Tallarico et al., 2016/2017, used a corticocancellous heterologous bone graft (OsteoBiol Gen-Os; Tecnoss srl, Giaveno, Italy) [23,24]. Of the xenografts, four of these documented a 100% survival rate for the IPR group [21,22,34,35,40] and one study documented 100% survival in the IPDL groups [23,24]. Overall, the survival rate ranged from 91.3 to 100%. Three studies used a mixture of autograft and xenograft (Bio-Oss^®; Geistlich Pharma AG, Wolhusen, Switzerland) and the survival rate ranged from 96.7 to 100% [38,39,50]

Autografts were used by three studies, two with IPR groups with survival rates of 80% [25] and 96.7% [25,41] and one with an IPDL survival rate of 84% [48]. The survival rate of autografts ranged from 80 to 100%. Allografts were also used by three studies. Block et al. [28] reported a 84.6% rate in IPR, Koh et al. [46] reported 95.5% in IPDL, and Shibly et al. [27] who used sterile, demineralized, freeze-dried bone (OraGRAFT, LifeNet Health, Virginia Beach, VA, USA) reported 96.6% and 93.3% for IPL and IPDL, respectively [27]. The survival rate for allografts ranged from 84.6 to 96.6%. Hydroxyapatite alloplasts (Sintlife, Faenza, Italy) and (Biosite; Vebas, Milan, Italy) were incorporated in two studies [29,47]. Cucchi et al., 2017, used the alloplast B-tricalcium phosphate (Oxofix, Biotec BTK, Dueville, Vicenza, Italy, BTK Italy) [44]. Alloplasts were revealed to have 95.5–100% survival rates. The studies are listed on

Table 12. Studies listed by bone graft type.

	No Bone Graft	Xenografts	Mixture of Autograft and Xenograft	Autografts	Allografts	Alloplasts
	Cecchinato et al., 2015, [42]	Canullo et al., 2009/2017, [21,22]	Pieri et al., 2011, [38]	Cannizzaro et al., 2010, [25]	Block et al., 2009, [28]	Canullo et al., 2010, [29]
	Cordaro et al., 2009, [43]	De Angelis et al., 2011, [45]	Slagter et al., 2015, [39]	Urban et al., 2012, [48]	Koh et al., 2011, [46]	Cucchi et al., 2017, [44]
	Crespi et al., 2008, [49]	De Rouck et al., 2009, [30]	Van Nimwegen et al., 2018, [50]	Zuiderveld et al., 2018, [41]	Shibly et al., 2012, [27]	Prosper et al., 2003, [47]
	Degidi et al., 2014, [31]	Esposito et al., 2015, [32]
	Palattella et al., 2008, [37]	Felice et al., 2015, [33]
		Grandi et al., 2014, [34]
		Migliorati et al., 2015, [35]
		Tallarico et al., 2016/2017, [23,24]
		Yoshino et al., 2014, [40]
Survival rates	95–100%	91.3–100%	96.7–100%	40–96.7%	84.6–96.6%	95.5–100%

.

4.8. Implants System/Geometry

All implants were titanium implants, except Cannizzaro et al. who used zirconia implants [25]. Tapered implants were the most common feature found in nine studies, with survival rates ranging from 91.3 to 100%. Four of the tapered implant studies reported 100% survival, all of which were in the IPR group [31,34,35,37]. Eight studies involved platform-switching implants. All survival rates were greater than 91.3–100%. Seven studies used wide or ultra-wide diameter implants and scored a survival rate between 83.7 and 100%. Tallarico et al., 2016/17, used wide implants and reported 100% in both its IPDL and DP groups [23,24]. Likewise, Prosper et al., 2003 also showed 100% survival in IPDL [47]; however Urban et al. noted a 83% survival rate and Cecchinato et al., 2015, reported 98.9% for the IPDL group [48]. Canullo et al., 2009/2016, and Canullo et al., 2010, both had 100% survival rates for the IPR group [21,22,29]. The studies are listed in

Table 13. Studies divided based on implant system and geometry.

	Zirconia Implants	Titanium Implants
	Standard Implant	Tapered Implants	Platform-Switching Implants	Wide/Ultra-Wide Diameter Implants
	Cannizzaro et al., 2010, [25] #	Cordaro et al., 2009, [43]	Canullo et al., 2009/2017, [21,22] *	Canullo et al., 2009/2017, [21,22] *
		De Angelis et al., 2011, [45]	Canullo et al., 2010, [29] *	Canullo et al., 2010, [29] *
		Degidi et al., 2014, [31] *	Cucchi et al., 2017, [44]	Cecchinato et al., 2015, [42]
		De Rouck et al., 2009, [30]	De Angelis et al., 2011, [45]	Felice et al., 2015, [33]
		Esposito et al., 2015, [32]	Grandi et al., 2014, [34] *	Prosper et al., 2003, [47] *
		Grandi et al., 2014, [34] *	Pieri et al., 2011, [38]	Tallarico et al., 2016/2017, [23,24] *
		Koh et al., 2011, [46]	Tallarico et al., 2016/2017, [23,24] *	Urban et al., 2012, [48] #
		Migliorati et al., 2015, [35] *	Yoshino et al., 2014, [40] *
		Palattella et al., 2008, [37] *
Survival rate ranges	40–80%	91.3–100%	91.3–100%	83.7–100%

Asterisk (*) indicates studies with 100% survival rates in at least one experimental group. Hashtag (#) indicates studies with survival rates below 90% in at least one experimental group.

.

4.9. Location of the Implant

Eighteen RCTs placed implants in the maxilla only, where eleven reported survival rates of 100%, six reported survival rates between 92 and 98.9%, and one RCT in the IPR group reported a survival rate of 84.6% [28]. Two out of the eighteen RCTs placed immediate implants in the maxillary anterior region only. Both studies reported 100% survival rates for IPR and DP implants. Five studies reported survival rates of IPR implants in the aesthetic zone (14–24), where three of the studies reported 100% survival rates and the other two reported 96.7% survival rates. Ten studies also included the second premolars. Six out of the ten RCTs reported 100% survival rates for the IPR group. The lowest survival rate for IPR implants involving maxillary anterior and premolar teeth was 84.6% reported by Block et al. [28]. The study also reported a 96.6% survival rate for the IPDL group. One other RCT only involved the maxillary posteriors and reported a survival rate for IPDL implants of 98.9%.

Eight RCTs involved placement of implants in both arches. Two RCT reported 100% survival rate for both IPDL and DP implants replacing posterior teeth. Cucchi et al. also noted similar results for DP posterior implants; however, the IPDL implants survival rate was only 95.5% [44]. Three other RCTs reported survival rates between 91.3 and 96.6% for IPDL posterior implants. One other study [25] investigated IPL, IPR, and DP implants involving both arches and reported survival rates of 40%, 80%, and 97%, respectively. The lowest survival rate for IPDL posterior implants was 83.7% [48]. The studies are listed on

Table 14. Studies divided based on location of the implants in the jaw.

	Maxillary Aesthetic Zone (14–24)	Premaxilla (15–25)	Maxillary Anterior (13–23)	Maxillary Posterior	Both Maxilla and Mandible
	Migliorati et al., 2013, [35] *	Block et al., 2009, [28] †,#	Degidi et al., 2014, [31] *	Pieri et al., 2011, [38] †	Cucchi et al., 2017, [44] *,†
	Slagter et al., 2015, [39] *	Canullo et al., 2009/2017, [21,22] *	Palatella et al., 2008, [37] *		Prosper et al., 2003, [47] *
	Van Nimwegen et al., 2018, [50] †	Canullo et al., 2010, [29] *			Tallarico et al., 2016/2017, [23,24] *
	Yoshino et al., 2014, [40] *	Cecchinato et al., 2015, [42] †			Urban et al., 2011, [48] #
	Zuiderveld et al., 2018, [41] †	Crespi et al., 2008, [49] *			Cannizzaro et al., 2010, [25] #
		De Rouck et al., 2009, [30] †			Cordaro et al., 2009, [43] †
		Esposito et al., 2015, [32]			De Angelis et al., 2011, [45] †
		Felice et al., 2015, [33]			Shibly et al., 2012, [27] †
		Grandi et al., 2014, [34] *
		Koh et al., 2014, [46] †
Survival Rate Ranges	96.7–100%	84.62–100%	100%	97.40%	40–100%

Asterisk (*) indicates studies with 100% survival rates in at least one experimental group. Obelisk (†) indicates studies reporting survival rates between 91.3 and 98.9% in at least one experimental group. Hashtag (#) indicates studies with survival rates between 80 and 84.6% in at least one experimental group.

.

5. Discussion

This systematic review analysed 26 randomised controlled trials to evaluate the survival rates of immediately placed single implants and describe the reasons for failure.

After analysis of the included articles, the survival rate of immediate single implants, regardless of loading, ranged from 40 to 100% over an average follow-up period of 24 months (range 12–120 months). One study that produced a drastically low survival rate of 40% for IPL and 80% for IPR was excluded as an outlier due to limitations, such as low sample size of IPL implants (n = 5), the use of zirconia implants, and that only one out of the four clinicians involved in the study had experience with zirconia implants [25]. After exclusion of this outlier, the survival rate range is 83.7–100%. Eleven RCTs presented with 100% survival rates in immediate implants. Similar to other reviews [10,11,13], most of the studies that were included in this review reported survival rates above 90%, except for three studies that reported survival rates of immediate implants ranging from 40 to 84.6% [25,28,48].

A previous systematic review on single immediate implants found a survival rate ranging between 94 and 100%, which is higher than our present study [14]. However, they included studies with a follow-up of less than a year. There was also a recent meta-analysis on single immediate implants, which resulted in a survival rate of 94.9% over a follow-up period of 12–96 months [13]. Two other meta-analyses on immediate implants also found similar survival rates, however they did not differentiate the results for single and multiple-units. Lang et al. [10] found a 2-year survival rate of 98.4% and a 4-year survival rate of 97.5%. Mello et al. [9] found a survival rate of 95.2% over a follow-up period of 6 months; however, they did not define ‘survival’, whereas the other reviews defined survival as the presence of the implant in the mouth, in accordance with the present review.

Most studies reported implant failure before placement of the definitive prosthesis and the main reason was failure of osseointegration, which is consistent with a previous systematic review [13]. Failure of osseointegration is commonly assessed by: clinical mobility of the implant, radiolucency between implant and bone, and the sound when a metal instrument taps the implant [389]. Two studies did not name a reason for implant failure, including Block et al. that reported a survival rate below 90% for IPR implants [28,46]. According to the study by Levin, a failure of osseointegration is typically due to overheating, trauma and contamination during surgery, lack of primary stability, micromotion, and overloading [390].

Of the 11 studies with 100% survival rates for immediate implants, the only consistent trend is the use of titanium implants and an amoxicillin antibiotic regime either pre- and/or post-operatively [21,22,23,24,26,29,31,34,35,37,39,40,47]. The preference for placement of implants in the maxilla and the use of grafting was also observed among these studies. Furthermore, the 100% survival rate trend may also be reflective of additional factors, such as operator experience and reporting bias.

In the study by Urban et al., 15 out of 92 implants failed [48]. A total of 11 out of the 15 failed implants were placed after tooth extraction due to apical periodontitis; however, the study did not utilise post-operative antibiotics nor did they debride the socket prior to the insertion of the implant. Most studies reporting high survival rates in apically infected sites debrided the extraction socket prior to insertion and implemented a post-operative antibiotic therapy to prevent bacterial transmission to the implant site [7,391]. Moreover, Urban et al. did not exclude smokers and used bone grafts in all implants [48], and previous studies have found significantly higher rates of implant failure in patients who smoke cigarettes, especially in those patients with bone grafts [392].

The effect of smoking on implant failure has been well-documented in the literature. Nicotine in cigarette smoke is detrimental to healing and osseointegration of implants [392,393]. On the other hand, smoking did not seem to play a visible role in survival in our current review, as similar survival rates were found in studies that included smokers in the inclusion criteria as compared to those that excluded them. It was noted that most studies either included smokers of less than or equal to ten cigarettes per day (n = 10) or did not exclude smoking (n = 10) (See Table 4). Not excluding smokers makes it difficult to discern the true number of smokers in the study and may hide the true impact of smoking on implant survival rates. Other than smoking, most studies tended to have stringent inclusion criteria and included only optimal situations where the patients are systemically healthy, and the site of implant placement has sufficient bone and lack of infection. The present study did not observe other patterns related to the remaining inclusion criteria.

The setting of a study may indicate the presence of factors that influence the results, such as operator experience and potential reporting bias. Of the included studies, there were an almost equal number of studies from private practices and universities, with three done in unknown settings. If the study by Cannizarro et al. [25] was excluded as an outlier, private practice survival rates ranged from 91.3 to 100%, whereas it ranged from 92 to 100% in universities. As both settings yielded similar results, bias arising from operator experience and selective reporting may be minimal.

Out of the 26 RCTs included in this study, only 3 investigated IPL implants [25,113,375]. Even though IPL implants significantly shorten treatment time, definitive prosthetic rehabilitation of an implant earlier than 3–4 months has not been recommended in the literature as it may jeopardise its stability [25,272,394,395]. Loading the implant with occlusal forces before complete healing can create micromotion which can prevent osseointegration and production of a fibrous scar tissue between the implant and bone [394]. This is supported by the high failure rate of IPL implants reported by Cannizarro et al. [25]. On the contrary, if the study by Cannizarro et al. [25] is excluded as an outlier, this review found that IPL implants have excellent results with survival rates of 96.6–100%. Even though this was concluded from a small sample size of two RCTs [27,113], this is supported by the findings from a previous systematic review that found a survival rate of 95.6% [396].

DP implants that were immediately loaded or loaded one week after placement also showed excellent survival rates, suggesting this may be a suitable treatment alternative. Again, as this was founded only on two RCTs [25,44], there is not enough evidence to corroborate the findings. Nevertheless, other studies have reported similar results [272,397].

Providing immediate non-occluding provisional restoration on the same day as implant placement is more desirable, as the patient does not have to be left without a tooth during the healing period while avoiding overloading the implants. Even though the provisional restorations can introduce micromovements that may interrupt osseointegration [398], immediate provisionalisation of post-extractive implants have been described as a reliable technique [36]. The current review found that IPDL implants have similar survival rates compared to IPR implants, where the survival rates for each group ranged from 83 to 100% and 80 to 100%, respectively.

According to the literature, the highest rate of implant failure was reported with post-extraction implants placed in the posterior maxilla due to poorer bone quality and the location of the base of maxillary sinus, which prevents the implant from achieving primary stability [224,399]. In agreement with this, the included studies that only placed IPDL implants in the posterior regions of both arches reported that most of the lost implants were placed in the posterior maxilla [44,48].

The majority of the RCTs that placed implants in the premaxillary zone achieved 100% survival rates, indicating that implants placed in this area can have predictable outcomes. According to the current review, IPR implants placed in the anterior maxilla only achieved 100% success rates. However, there were only two RCTs that exclusively placed implants in the anterior maxilla [31,37].

Interestingly, of the four studies that did not restrict the location of implant placement, none reported a 100% survival rate [25,27,43,45]. From these four studies, two failed implants replaced the mandibular second premolar [25,27]. The posterior mandible often receives heavy masticatory forces during function which may contribute to failure of these implants [399]. Furthermore, the height between the mandibular canal and the alveolar crest often limits the length of the implant which may be insufficient to achieve primary stability [399]. Hence, careful case selection and planning is required when placing implants in this area. Most of the included studies did not report the location of the lost implants, hence further investigation is required.

There is contradicting evidence on the benefits of antibiotics in implant therapy [10,13,400,401,402,403,404,405]. Furthermore, problems including antibiotic resistance and allergies can arise. Among the studies in the current review, only two studies [42,43] did not use an antibiotic regimen but both yielded high survival rates (96.6–98.9%). Whereas the studies yielding low survival rates used an antibiotic regimen. Hence, this review could not conclude that higher survival rates are solely due to the use of antibiotics.

There has been evidence that pre-operative antibiotics reduce early implant failure, by reducing the amount of bacteria in the surgical site [403,406,407,408,409]. On the other hand, the evidence on the benefit of post-operative antibiotics on implant therapy has been unclear [406,408]. In immediate implants, however, two systematic reviews found that the prescription of pre- and post-operative or only post-operative antibiotics significantly reduced early implant failure, especially when compared to use of pre-operative antibiotics only [10,13]. The present review found that half of the studies prescribing antibiotics used it both pre- and post-operatively. It was noted that none of these studies had survival rates below 90%, suggesting that there may be some benefit to this regimen. However, this suggestion should be treated with caution considering that only four of the eleven studies with 100% survival rates used this regimen.

In terms of the type of antibiotic, amoxicillin was the most commonly used (n = 21) and was used by all studies achieving 100% survival rates. Two of the three studies achieving survival rates less than 90% did not use amoxicillin as an antibiotic [28,48]. Hence, when antibiotics are used, amoxicillin may achieve higher survival rates. Another study also found amoxicillin as the most frequently prescribed antibiotic after implant placement [410]. Its efficacy is likely due to its moderate spectrum that encompasses odontogenic bacteria, along with an acceptable dosing schedule for good patient compliance [411]. There is limited data in the present review about the efficacy of alternative antibiotics for IIP in the case of a penicillin allergy. Clindamycin was used as an alternative to amoxicillin in only six studies [25,32,33,35,41,45], and clarithromycin and azithromycin were only used in one study each [34,46].

The use of bone grafts did not appear to influence survival rates in the studies which used bone grafts compared to those that did not. However, there is a consensus in the literature that bone grafts are advantageous in the inhibition of peri-implant bone loss in immediate extraction sockets [412]. When comparing the survival rates of the present included studies using autografts and allografts to other graft materials, xenografts and alloplasts had more consistently high survival rates. The accelerated resorption rates of autografts have made other grafting materials more desirable as they do not completely resorb and so the stability is retained long-term [413]. Another retrospective study using both immediate and delayed implants found the clinical survival rate for autografts to be 94.4–97.9% within a two-year follow-up, compared to 100% for bovine xenografts [414].

In the present study, only 1 in the 26 studies used zirconia implants, which is likely due to the lack of long-term data compared to the well-researched titanium implant [415]. Zirconia is an attractive alternative as it is said to attract less bacterial plaque, produce a low inflammatory infiltrate, and provide good tissue integration, which makes it desirable in limiting peri-implant biological complications [415]. However, a systematic review and meta-analysis with immediate and delayed placement of zirconia implants reported a 92% survival rate after one year whereas titanium implants boasted 97% after five years [416]. It is possible that the use of zirconia implants in the study by Cannizarro et al. [25] contributed to its poor survival rate.

Tapered implants were a popular design choice amongst the studies. The larger diameter threads at the coronal portion compared to the tapping portion led to better bone compaction at the crest at which the implants were placed [417]. This improved primary stability and may prevent early failure as seen in the nine studies using tapered implants, all reaching a survival rate of 100%. Platform-switching was the second most common design and is likely attributed to the numerous studies that have supported the significant reduction in peri-implant marginal bone loss [418,419]. The literature has reported that the survival rates between platform-switching implants and platform-matching implants were comparable and the type of platform was not considered to be the determinant of implant survival [419]. For the studies that used titanium implants only, the survival rates of platform-switched implants ranged from 91 to 100% whilst the survival rates for platform-matched implants ranged from 84 to 100% which suggests that platform-switching may influence survival. Wide diameter implants, defined as ≥4.5 mm (Renouard and Nisand 2006), presented mostly 100% survival rates (seven out of eight studies) [418]. Its ability to close the implant socket gap and engage more bone makes it easier to achieve primary stability, which reduces the need for bone grafts [23,419]. The wide diameter also prevents the implants from being overloaded which can diminish osseointegration [419]. A meta-analysis has reported that wide implants had a strong survival rate of 92% after five years [419].

The limitations of the studies are as follows. First, most of the included studies were of an unclear risk of bias and eight had a high risk of bias. Secondly, other confounding factors such as follow-up period and the patient history could present heterogeneity amongst the included studies. Finally, the small number of samples per placement or loading category makes it difficult to draw definitive conclusions.

6. Conclusions

This systematic review investigated 26 randomised control trials and found a survival rate of 83.7–100% for single immediately placed implants. Implant failure was not consistently reported and when reported, failure due to lack of osseointegration prior to placement of the definitive restoration was the most common descriptor. Others attributed reasons included infection abscess, mobility after immediate loading, and iatrogenic complication. Several factors may influence the survival of immediate implants, such as loading protocols, location of implants in the jaw, antibiotic protocol, grafting methods, and implant geometry; however, the current literature lacks a large volume of homogenous studies reporting on immediately placed implants and so further investigation is required.