| Table 1. Characteristics of the studies included. | |||||||
| Author | Country | Study Period | Design | Intervention | Control Group | Study Group | |
|---|---|---|---|---|---|---|---|
| Baart et al., 2007 | Netherlands | Dec'02-Aug'05 | RCT | Low vs. Conventional Stimulation | 150 IU / antagonist | 225 IU / long agonist | |
| Weghofer et al., 2008 | Austria/USA | Jan'04-Jun'05 | Retrospective | FSH vs. LH-containing gonadotropins/agonist protocol | FSH | hMG | |
| Verpoest et al., 2008 | Belgium | Oct'05-Apr'06 | Prospective observational study | Aneuploidy in Unstimulated Cycles | No control group | Unstimulated cycles | |
| Haaf et al., 2009 | Germany | Jan'02-Dec'05 | Retrospective | Oocyte aneuploidy by age and response (1-5, 6-10, or >10 oocytes) | <35 years | 35-40 years; >40 years | |
| Weghofer et al., 2009 | Austria/USA | Jan'03-Jun'05 | Retrospective | FSH vs. LH-containing gonadotropins/antagonist protocol | FSH | hMG | |
| Rubio et al., 2010 | Spain | NA | Crossover study | 1st cycle normal dose vs. 2nd cycle 30% reduce dose, 3 months apart | 225 IU/long agonist | 150 UI/antagonist | |
| Kyrou et al., 2011 | Belgium | Oct'92-Dic'06 | Retrospective | GnRH agonist vs. GnRH Antagonist | Agonist | Antagonist | |
| Massie et al., 2011 | USA | Jan'99-Aug'07 | Retrospective | Aneuploidy in miscarriages from stimulation vs. no stimulation | Natural conceptions | Stimulation | |
| Ata et al., 2012 | USA | Jan'10-Jul'11 | Retrospective | Aneuploidy according to embryos biopsied | NA | NA | |
| Labarta et al., 2012 | Spain | Sep'06-Mar'10 | Prospective crossover study | 1st cycle unstimulated vs. 2nd cycle stimulated, same patient | Unstimulated | Stimulated with 225 IU | |
| Sekhon et al., 2017 | USA | Mar'10-Apr'15 | Retrospective | Cumulative dose and aneuploidy rate | NA | NA | |
| Labarta et al., 2017 | Spain | Sep'06-Mar'10 | Post hoc analysis of prospective crossover study | Aneuploidy according to ovarian response (same-dosage): low vs. high | Low: <17 oocytes | High: ≥17 oocytes | |
| Barash et al., 2017 | USA | Jan'13-Jan'13 | Retrospective | Different dosages of gonadotropins and aneuploidy rate | NA | NA | |
| Venetis et al., 2019 | Australia | Mar’11-Dec’16 | Retrospective, Multicenter | Correlation of oocytes retrieved and the number of euploid embryos | NA | NA | |
| Thorne et al., 2019 | USA | Jan’13-Feb’18 | Retrospective | Final oocyte maturation trigger rhCG vs. aGnRH | rhCG trigger | aGnRH trigger | |
| Author | Inclusion Criteria | Patients | Patients by Group | PGT platform | Biopsy Day | Cells Biopsied | Cells Biopsied |
| Baart et al., 2007 | General IVF patients, regular menses, 5 mill sperm, 46XX | 111 | Low=67 High=44 |
FISH (10 chromosomes) | Day 3 | Cells Biopsied | Low=33.2 High=34.1 |
| Weghofer et al., 2008 | General IVF patients, regular menses, normal ovarian function, 46XX | 104 | FSH=52 hMG=52 |
FISH (9 chromosomes) | Day 3 | 1-2 cells | FSH=35.0 hMG=35.9 |
| Verpoest et al., 2008 | Regular menses, <3 failed cycles, normal uterine cavity | 30 | Unstimulated=30 | FISH (5 chromosomes) | Day 3 | 1 cell | 31.4 |
| Haaf et al., 2009 | >35 years or previous IVF cycle with no ET | 30 | <35: 93 cycles 35-40: 376 cycles >40: 165 cycles |
FISH (5 chromosomes) | Day 0 | 1 cell | NA |
| Weghofer et al., 2009 | General IVF patients, regular menses, normal ovarian function, 46XX | 104 | FSH=52, hMG=52 | FISH (9 chromosomes) | Day 3 | 2 cells | FSH=39.8 hMG=39.6 |
| Rubio et al., 2010 | Oocyte donors | 32 | First cycle= 32 Second cycle=22 (10 no biopsy) |
FISH (9 chromosomes) | Day 3 | 1 cell | 22.0 |
| Kyrou et al., 2011 | Recurrent Miscarriage, RIF, azoospermia | 694 | Agonist=320 Antagonist=374 |
FISH (7 Cells Biopsied) | Day 3 | 1-2 cells | Agonist=32.8 Antagonist=32.7 |
| Massie et al., 2011 | Infertility patients trying to conceive | 229 | No stimulation=50 FSH for IUI=35 FSH for IVF=144 |
Trypsin-Wright G-banding | NA | 1 cell | Natural 37.0 FSH exposure 37.0 |
| Ata et al., 2012 | Infertility patients undergoing PGT or Oocyte donors | 990 | 7753 embryos | aCGH-based CCS | Day 3/Day 5 | POCs | NA |
| Labarta et al., 2012 | Oocyte donors | 232 | Unstimulated=185 Stimulated=47 |
FISH (9 chromosomes) | Day 3 | Day 3: 1-2 cells; Day 5: 3-10 cells |
25.4 |
| Sekhon et al., 2017 | Infertility patients undergoing PGT | 828 | 1122 cycles | qPCR-based CCS | Day 5 | 1 cell | 38.5 |
| Labarta et al., 2017 | Oocyte donors | 46 | Low response=22 High response=24 |
FISH (9 chromosomes) | Day 3 | 4-7 cells | Low=25.6 High=24.9 |
| Barash et al., 2017 | Infertility patients undergoing PGT | 681 | 794 cycles | SNP | Day 5 | 4-9 cells | NA |
| Venetis et al., 2019 | Infertility patients undergoing PGT | 724 | 724 cycles | aCGH | Day 3 | 1 cell | NA |
| Thorne et al., 2019 | Infertility patients undergoing PGT | 539 | hCG trigger=336 aGnRH trigger=203 |
aCGH/NGS | Day 5 | NA | No restriction |
| Author | Primary Outcome measure | Oocytes retrieved | Aneuploidy Rate per embryo | Aneuploidy Rate by ITT | Euploid Embryos (n) | Euploid Embryos by ITT (n) | |
| Baart et al., 2007 | Oocytes retrieved Aneuploidy Rate |
Low=8.2 High=12.1 |
Low=50% High=62%, p=0.48 |
Low=22% High=26%, p=0.4 |
Low=1.8 High=1.8 |
Low=1.4 High=2.5 |
|
| Weghofer et al., 2008 | Oocytes retrieved Aneuploidy Rate |
FSH=23.7 hMG=20.3 |
FSH=54.7% hMG=30.2%, p<0.01 |
Only patients with biopsy included | FSH=3.1 hMG=3.3 |
NA | |
| Verpoest et al., 2008 | Aneuploidy Rate | Unstimulated =0.6 | Unstimulated=36.4% | NA | Unstimulated =0.2 | NA | |
| Haaf et al., 2009 | Aneuploidy per cohort size (1-5,6-10, >10 oocytes) and per age (<35, 35–40, >40) | <35: 8.5 35-40: 8.6 >40: 7.1 |
1-5 oocytes (<35: 23.3%; 35-40:41.2%; >40:49.6%) 6-10 oocytes (<35:34.9%; 35-40: 43.8%; >40: 50.0%) >10 oocytes (<35:50.9%; 35-40:54.6%; >40:54.1%) | NA | NA | NA | |
| Weghofer et al., 2009 | Oocytes retrieved Aneuploidy Rate |
FSH=15.2 hMG=13.8 |
FSH=70.6% hMG=74.3%, NS |
NA (only patients with biopsy included) | FSH=2.1 hMG=1.9 |
NA | |
| Rubio et al., 2010 | Oocytes retrieved Aneuploidy Rate |
Standard=23.9 Reduced=14.7 |
Standard=83.9% Reduced=77.5% |
NA | Standard=3.1 Reduced=2.7 |
Standard=3.1 Reduced=1.8 |
|
| Kyrou et al., 2011 | Oocytes retrieved Aneuploidy Rate |
Agonist=12.9 Antagonist=13.6 |
Agonist=49.9% Antagonist 50.2%, p=0.922 |
NA (only patients with biopsy included) | Agonist=2.7 Antagonist=3.1 |
NA | |
| Massie et al., 2011 | Aneuploid gestation | NA | Natural=70% FSH exposure=63%, NS |
NA | NA | NA | |
| Ata et al., 2012 | Aneuploidy per cohort size (1-4, 5-7, 8-10, >10 embryos) and per age (<35, 35–39, 40–42, ≤43) | NA | Per age and (D3/Blastocyst): <35 (38.3%/61.4%) 35–39 (28.9%/50.27%) 40–42 (16.05% /33.37%); ≤43 (8.95%/17.3%) | NA | NA | NA | |
| Labarta et al., 2012 | Aneuploidy Rate | Unstimulated =0.8 Stimulated=17.8 |
Unstimulated=35.3% vs. Stimulated=40.6% | Unstimulated =76.7% Stimulated =40.6% |
Unstimulated =1.8 Stimulated=3.9 |
Unstimulated =1.0 Stimulated=3.9 |
|
| Sekhon et al., 2017 | Cumulative gonadotropin dose used, duration of stimulation | NA | 47% no association of cumulative dose and aneuploidy (adjusted OR=1.0.49, p=0.232) | NA | NA | NA | |
| Labarta et al., 2017 | Number of euploid embryos | Low=11.5 High=23.8 |
Low=39% High=639%, p=0.2 |
NA | Low=2.7 . High=5.0 |
NA | |
| Barash et al., 2017 | Aneuploidy Rate per dosage and per age | 16,3 | <35 years old: 62.86% 35–37 years old: 55.75% 38-40 years old: 42.23% >41 years old: 27.53% |
NA | NA | NA | |
| Venetis et al., 2019 | Number of euploid embryos | 11.7 (11.1–12.2) | Euploidy 17.4% (15.5–19.3), Aneuploidy 82.6% | NA | 1.0 (0.9–1.1) | NA | |
| Thorne et al., 2019 | Aneuploidy Rate | hCG=11.5 aGnRH=19.3 |
hCG=30.3% vs
. aGnRH=37.8% MLRA: no differences between groups |
NA | NA | NA | |
*RCT: randomized controlled trial; IU: international units; USA: United States of America; FSH: follicle stimulating hormone; LH: luteinizing hormone; hMG: human menopausal gonadotropins; NA: not applicable; GnRH: gonadotropin-releasing hormone; rhCG: recombinant human chorionic gonadotropin; aGnRH: agonist of the GnRH; IVF: in vitro fertilization; FISH: Fluorescence in situ hybridization; RIF: repeated implantation failure; IUI: intrauterine insemination; POCs: products of conception; PGT: preimplantation genetic testing; array comparative genomic hybridization; qPCR-based CCS: quantitative polymerase chain reaction – based comprehensive chromosome screening; SNPs: single nucleotide polymorphism; NGS: next-generation sequencing; ITT: intention-to-treat; D3: cleavage-stage embryo.