Table 1.
Study characteristics.
| No. | References | Country | Study type | Study period | Study population | Oocyte activation protocol | Control | Cases number | Outcome indicators |
|---|---|---|---|---|---|---|---|---|---|
| 1 | Li J. et al. (2019) | China | Sibling oocytes control study-prospective cohort study | Oct 2015–Dec 2017 | Previous ICSI cycles of no or low fertilization or were diagnosed with severe teratozoospermia | Calcium ionophore (ionomycin) exposure twice for 5 min with a 30 min interval | Sibling oocytes | 50 patients Survival MII oocytes after ICSI: 513 oocytes AOA: 262 oocytes; control: 251 oocytes |
Fertilization rate, Cleavage rate, blastocyst rate, Implantation rate, Pregnancy rate, Live-birth rate, Abortion rate, Fetal defect |
| 2 | Bonte et al. (2019) | Belgium | Retrospective cohort study | Apr 2001–Apr 2018 | Previous ICSI cycles of no or low fertilization (≤33.3%) | CaCl2 injection and Calcium ionophore (ionomycin) exposure twice for 10 min with a 30 min interval | Before-after self contrast | 122 couples AOA: 191 cycles, 2,476 oocytes; control: 243 cycles, 2351 oocytes | Fertilization rate, Pregnancy rate, Live-birth rate, Abortion rate, Fetal defect |
| 3 | Li B. et al. (2019) | China | Retrospective cohort study | Jan 2011–Dec 2016 | (1) ICSI fertilization rate ≤50; (2) good quality embryo rate ≤30%; (3) severe oligoasthenoteratozoospermia (OAT); (4) TESA or PESA | Calcium ionophore (ionomycin) exposure for 10 min | Conventional ICSI | AOA:169 patients control:507 patients | Implantation rate, Pregnancy rate, Live-birth rate, Abortion rate, Fetal defect |
| 4 | Fawzy et al. (2018) | Egypt | RCT | Apr 2015–Jan 2016 | Two previous ICSI cycles of low fertilization (0–30%) or with male-factor infertility undergoing their first ICSI cycle | Group I (SrCl2 for 60 min post-ICSI) group II (GM508 CultActive for 20 min post-ICSI) | Randomized controlled | 343 participants (SrCl2 AOA:115, calcimycinAOA:113 and ICSI:115) | Fertilization rate, Cleavage rate, top Embryo rate, Blastocyst rate, Implantation rate, Pregnancy rate, Live-birth rate, Abortion rate |
| 5 | Mateizel et al. (2018) | Belgium | Single-center observational study- prospective cohort study | 2004–2015 | Low (n = 14) or no (n = 16) fertilization in previous cycles, globozoospermia (n = 6), small acrosome (n = 2), and poor embryo development (n = 1) | CaCl2 injection and Calcium ionophore (ionomycin) exposure twice for 7 min with a 30 min interval or calcium ionophore (GM508 CultActive) exposure for 15 min | Conventional ICSI | 237 cycles, 74 pregnancies with ICSI+AOA, 47 newborns. | Fetal defect |
| 6 | Miller et al. (2016) | Israel | Retrospective cohort study | 2006–2014 | Failed fertilization after one ICSI procedure in the presence of at least five mature oocytes without oocyte abnormality or had <10% fertilization rate | Calcium ionophore (A23187) exposure for 10 min | Conventional ICSI | AOA: 83 pregnancies; ICSI: 595 pregnancies. | Abortion rate, fetal defect |
| 7 | Aydinuraz et al. (2016) | Turkey | Prospective, randomized and single blind study | Dec 2013–Feb 2014 | Teratozoospermia (<4% according to WHO 2010 reference limits) and a low fertilization rate (<50%) in the previous cycle | Calcium ionophore (GM508 CultActive) exposure for 15 min | Sibling oocytes | 21 couples AOA: 97 MII oocytes; Control: 97 MII oocytes |
Fertilization rate, cleavage rate, top embryo rate, implantation rate, pregnancy rate, live-birth rate, abortion rate |
| 8 | Dayong Hao et al. (2016) | China | Sibling oocytes control study | Jan 2015–Dec 2015 | Previous ICSI cycles of low fertilization ≤30%, globozoospermia, or poor embryo development | Calcium ionophore (A23187) exposure for 15 min | Sibling oocytes | AOA: 12 patients; ICSI: 12 patients | Fertilization rate, top embryo rate, fetal defect |
| 9 | Ebner et al. (2015) | Germany/ Austria |
Prospective multicentre study | Duration almost 2-year | Previous ICSI cycles of low fertilization <50%, at least three cumulus–oocyte complexes | Calcium ionophore (GM508 CultActive) exposure for 15 min | Before-after self contrast | AOA: 101 cycles; Control: 101 cycles | Fertilization rate, blastocyst rate |
| 10 | Caglar Aytac et al. (2015) | Turkey | Prospective, randomized controlled study | Jan 2014–Aug 2014 | DOR and partners with normal sperm parameters | Calcium ionophore (GM508 CultActive) exposure for 15 min | Randomized controlled | AOA: 148 patients; Control: 148 patients | Fertilization rate, cleavage rate, pregnancy rate, live-birth rate |
| 11 | Kang et al. (2015) | Korea | Retrospective study | Jan 2006–Jun 2013 | Previous ICSI cycles of no or low fertilization (<45%) | Calcium ionophore (A23187) exposure for 5 min | Conventional TESE | AOA: 29 cycles; Control: 480 cycles | Pregnancy rate, live-birth rate |
| 12 | Ebner et al. (2014) | Austrian | Prospective, multicenter, uncontrolled intervention study |
Duration 1 year | Complete developmental arrest (no transfer), or complete developmental delay (no morula/blastocyst on Day 5), or significantly reduced blastocyst formation (≤15%) in a previous cycle | Calcium ionophore (GM508 CultActive) exposure for 15 min | Before-after self contrast | AOA: 57 cycles; Control: 57 cycles | Fertilization rate, cleavage rate, top embryo rate, blastocyst rate, implantation rate, pregnancy rate, live-birth rate, abortion rate, fetal defect |
| 13 | Deemeh et al. (2014) | Iran | Historical cohort study |
Feb 2008–May 2010 | (1) Testicular sperm extraction (TESE); (2) severe teratozoospermia (sperm with abnormal morphology ≥98%) |
Calcium ionophore (ionomycin) exposure for 10 min | Conventional ICSI | AOA-ICSI: 275 cycle (TESE: 150, severe teratozoospermia: 125); Control: 406 cycle |
Pregnancy rate, live-birth rate, abortion rate, fetal defect |
| 14 | Yoon et al. (2013) | America | Retrospective study | 2007–2011 | Previous ICSI cycles of no or low fertilization (≤50%) | Calcium ionophore (A23187) exposure for 30 min | Before-after self contrast | AOA: 185 cycles; Control: 185 cycles |
Implantation rate, pregnancy rate, live-birth rate, abortion rate, fetal defect |
| 15 | Eftekhar et al. (2013) | Iran | Prospective, randomized, unblinded, clinical trial |
Apr 2012–Dec 2012 | Teratoospermic partner (normal morphology <14%) undergoing to ICSI cycles |
Calcium ionophore(A23187) exposure for 5 min | Randomized controlled | AOA: 19 patients; ICSI:19 patients | Pregnancy rate, live-birth rate, abortion rate |
| 16 | Ebner et al. (2012) | Germany/ Austria |
Prospective multicenter study | Aug 2009–Mar 2011 | Patients with azoospermia (44%) or cryptozoospermia (56%) (e.g., showing <0.1 spermatozoa/mL) | Calcium ionophore (GM508 CultActive) exposure for 15 min | Before-after self contrast | AOA: 75 cycles; Control: 88 cycles | Fertilization rate, blastocyst rate, implantation rate, pregnancy rate, live-birth rate, fetal defect |
| 17 | Montag et al. (2012) | Germany | Retrospective cohort study | 2003–2009 | Patients with 0, 1–29, or 30–50% fertilization in a previous ICSI cycle | Calcium ionophore (A23187) exposure for 15 min | Before-after self contrast | AOA: 129 cycles; Control: 103 cycles | Fertilization rate, implantation rate, pregnancy rate, live-birth rate, abortion rate, fetal defect |
| 18 | Vanden Meerschaut et al. (2012) | Belgium | Prospective case series |
Jan 2006–Dec 2011 | Previous ICSI cycles of no or low fertilization in whom the MOAT >84% | CaCl2 injection and Calcium ionophore (ionomycin) exposure twice for 10 min with a 30 min interval | Sibling oocytes | AOA: 14patients Control: 14 patients |
Fertilization rate |
| 19 | Borges et al. (2009a) | Brazil | RCT | Jan 2006–Jul 2007 | (1) Testicular sperm aspiration in non-obstructive-azoospermic patients (TESA-NOA group, n = 58); (2) TESA in obstructive- azoospermic patients (TESA-OA group, n = 48); (3) and percutaneous epididymal sperm aspiration in obstructive-azoospermic patients (PESA-OA, n = 98) | Calcium ionophore (A23187) exposure for 30 min | Randomized controlled | TESA-NOA AOA: 29 cycles; Control: 29 cycles; TESA-OA control: 24 cycles; AOA: 24 cycles; PESA-OA control: 49 cycles; AOA: 49cycles |
Fertilization rate, top embryo rate, implantation rate, pregnancy rate |
| 20 | Borges et al. (2009b) | Brazil | RCT | Jan 2006–Jul 2007 | The ejaculated group (n = 92), the epididymal group (n = 82), and the testicular group (n = 140) | Calcium ionophore (A23187) exposure for 30 min | Randomized controlled | Ejaculated AOA: 46 cycles; Control: 46 cycles Epididymal; AOA: 41 cycles; Control: 41 cycles; Testicular AOA: 70 cycles; Control:70 cycles |
Fertilization rate, top embryo rate, implantation rate, pregnancy rate, abortion rate |
| 21 | Heindryckx et al. (2008) | Belgium | Prospective cohort study | None | Failed or low fertilization in previous ICSI cycles or who had well-known sperm-borne activation deficiencies such as globozoospermia | CaCl2 injection and Calcium ionophore (ionomycin) exposure twice for 10 min with a 30 min interval | Before-after self contrast | AOA: 30 patients; Control: 30 patients | Fertilization rate, pregnancy rate, live-birth rate, fetal defect |
| 22 | Kyono et al. (2012) | Japan | Retrospective study | 1 April 2004 and 31 October 2010 | Previous ICSI cycles of low fertilization (≤30%) | Group I (SrCl2 for 60–120 min post-ICSI) group II (A23187 5–10 min post-ICSI) | Fetal defect: conventional ICSI Fertilization rate/Pregnancy rate/Implantation rate/abortion rate: before-after self contrast | SrCl2: 35 patients A23187: 50 patients; Conventional ICSI: 530 patients |
Fertilization rate, pregnancy rate, implantation rate, abortion rate, fetal defect |