Obstetric and neonatal outcomes of pregnancies resulting from preimplantation genetic testing: a systematic review and meta-analysis

Abstract

BACKGROUND Preimplantation genetic testing (PGT) includes methods that allow embryos to be tested for severe inherited diseases or chromosomal abnormalities. In addition to IVF/ICSI and repeated freezing and thawing of the embryos, PGT requires a biopsy to obtain embryonic genetic material for analysis. However, the potential effects of PGT on obstetric and neonatal outcomes are currently uncertain. OBJECTIVE AND RATIONALE This study aimed to investigate whether pregnancies conceived after PGT were associated with a higher risk of adverse obstetric and neonatal outcomes compared with spontaneously conceived (SC) pregnancies or pregnancies conceived after IVF/ICSI. SEARCH METHODS PubMed, EMBASE, MEDLINE, Web of Science and The Cochrane Library entries from January 1990 to January 2021 were searched. The primary outcomes in this study were low birth weight (LBW) and congenital malformations (CMs), and the secondary outcomes included gestational age, preterm delivery (PTD), very preterm delivery (VPTD), birth weight (BW), very low birth weight (VLBW), neonatal intensive care unit (NICU) admission, hypertensive disorders of pregnancy (HDP), gestational diabetes, placenta previa and preterm premature rupture of membranes (PROM). We further pooled the results of PGT singleton pregnancies. Subgroup analyses included preimplantation genetic diagnosis (PGD), preimplantation genetic screening (PGS), cleavage-stage biopsy combined with fresh embryo transfer (CB-ET) and blastocyst biopsy combined with frozen-thawed embryo transfer (BB-FET). OUTCOMES This meta-analysis included 15 studies involving 3682 babies born from PGT pregnancies, 127 719 babies born from IVF/ICSI pregnancies and 915 222 babies born from SC pregnancies. The relative risk (RR) of LBW was higher in PGT pregnancies compared with SC pregnancies (RR = 3.95, 95% confidence interval [CI]: 2.32–6.72), but the risk of CMs was not different between the two groups. The pooled results for the risks of LBW and CMs were similar in PGT and IVF/ICSI pregnancies. The risks of PTD (RR = 3.12, 95% CI: 2.67–3.64) and HDP (RR = 3.12, 95% CI: 2.18–4.47) were significantly higher in PGT pregnancies compared with SC pregnancies. Lower gestational age (mean difference [MD] = −0.76 weeks, 95% CI −1.17 to −0.34) and BW (MD = −163.80 g, 95% CI: −299.35 to −28.24) were also noted for PGT pregnancies compared with SC pregnancies. Nevertheless, compared with IVF/ICSI pregnancies, the risks of VPTD and VLBW in PGT pregnancies were significantly decreased by 41% and 30%, respectively, although the risk of HDP was still significantly increased by 50% in PGT pregnancies compared with IVF/ICSI pregnancies. The combined results of obstetric and neonatal outcomes of PGT and IVF/ICSI singleton pregnancies were consistent with the overall results. Further subgroup analyses indicated that both PGD and PGS pregnancies were associated with a higher risk of PTD and a lower gestational age compared with SC pregnancies. WIDER IMPLICATIONS This meta-analysis showed that PGT pregnancies may be associated with increased risks of LBW, PTD and HDP compared with SC pregnancies. The overall obstetric and neonatal outcomes of PGT pregnancies are favourable compared with those of IVF/ICSI pregnancies, although PGT pregnancies were associated with a higher risk of HDP. However, because the number of studies that could be included was limited, more randomised controlled trials and prospective cohort studies are needed to confirm these conclusions.

Trophectoderm biopsy is associated with adverse obstetric outcomes rather than neonatal outcomes

“…Zhang et al [7] found a decreased odds of PPROM in the PGT group, but the difference was not signi cant (7.0 vs. 11.6%, aOR 0.63, 95% CI 0.28-1.42, P = 1.0). Moreover, other previous studies revealed comparable risks regarding PPROM [4,5,7,14,22,23]. However, there is a paucity of available data investigating maternal outcomes of PROM in PGT-induced pregnancies.…”

“…The unavailability of crucial baseline characteristics may render the conclusion credible. Moreover, two recent systematic reviews and meta-analyses suggested that PGT with TE biopsies was associated with a lower rate of VLBW [4,5]. These two studies are di cult to compare to our study, as they included studies with donor oocyte cycles, cleavage-stage biopsies, and fresh embryo transfers.…”

“…In regard to neonatal outcomes, blastocyst biopsy did not add additional risks following FET cycles [6][7][8][9][12][13][14]. In contrast to these observations, pregnancies conceived after PGT were associated with an increased risk of preterm birth [15] and decreased risks of very preterm birth (VPTB) [4,16] and very low birth weight (VLBW) [4,5], as indicated previously.…”

Endometrial thickness is associated with low birthweight in frozen embryo transfer cycles: A retrospective cohort study of 8,235 singleton newborns

“…On the one hand, some studies have shown that subfertility itself is the main reason for the adverse perinatal outcomes (3,4). On the other hand, growing evidence suggested that both ART procedures and embryo manipulation in the laboratory may play a vital role (5)(6)(7)(8). Furthermore, recent studies reported that endometrial thickness (EMT) could be involved as well.…”

Is telephone follow-up reliable in maternal and neonatal outcomes surveys in in vitro fertilization?

“…With the expanding use of ART, there is a rising concern regarding the safety of these treatments for both mother and child [3]. Hundreds of studies focused on the obstetric and perinatal outcomes of in vitro fertilization (IVF) treatment [4][5][6][7]. However, the incidences differed significantly between studies for the same maternal complication (e.g., gestational diabetes).…”