Pregnancy-related complications and adverse pregnancy outcomes in multiple pregnancies resulting from assisted reproductive technology: a meta-analysis of cohort studies

Risk of adverse pregnancy and perinatal outcomes after high technology infertility treatment: a comprehensive systematic review

“…In all meta-analytic data [16, 17, 22, 23] perinatal mortality was not increased. A recent cohort study [24], however, reported an adjusted risk of perinatal death for twins 45 and 85 % lower among ART births than fertile or subfertile births, respectively.…”

“…A recent meta-analysis including 39 cohort studies explored the risk of adverse pregnancy outcomes in ART conceptions compared with NC in a sample of 146,008 multiple births [22]. ART were associated with a higher risk of premature rupture of membranes (RR 1.20, 95 % CI 1.05 to 1.37), PIH (RR 1.11, 95 % CI 1.04 to 1.19), GDM (RR 1.78, 95 % CI 1.25 to 2.55), PTB (RR 1.08, 95 % CI 1.03 to 1.14), EPTB (RR 1.18, 95 % CI 1.04 to 1.34), LBW (RR 1.04, 95 % CI 1.01 to 1.07), and VLBW (RR 1.13, 95 % CI 1.01 to 1.25) when compared to NC [22].…”

“…ART were associated with a higher risk of premature rupture of membranes (RR 1.20, 95 % CI 1.05 to 1.37), PIH (RR 1.11, 95 % CI 1.04 to 1.19), GDM (RR 1.78, 95 % CI 1.25 to 2.55), PTB (RR 1.08, 95 % CI 1.03 to 1.14), EPTB (RR 1.18, 95 % CI 1.04 to 1.34), LBW (RR 1.04, 95 % CI 1.01 to 1.07), and VLBW (RR 1.13, 95 % CI 1.01 to 1.25) when compared to NC [22]. When data were restricted to matched and/or high quality studies, the risk of PIH, GDM, PTB, and LBW/VLBW increased further.…”

“…when estimating the effect of ART singletons on obstetric outcomes.- Patients who achieved a pregnancy with OI and IUI have been considered in the NC category.- Substantial heterogeneity among studies for association between ART singleton pregnancies and obstetric risks.- A number of the outcomes, especially for pregnancy-related complications, relied on between 2 and 7 of the 50 total studies.Cromi et al, 2016 [21]Case–control studyThe study reports the experience of a tertiary referral center; therefore, this factor may have inflated the observed rates of peripartum hysterectomy.The control populations have not been separated into two groups (normal fertile couples and infertile couples who conceive without treatment) to determine the degree to which observed associations are specifically related to the ART procedures vs. infertility per se.- Detailed information on the infertility treatments was not available.- Small study number.Pandey et al, 2012 [18]Review of 20 matched cohort studies and 10 unmatched cohort studiesAscertainment bias with the findings of increased complications with IVF/ICSI; i.e. women may be more anxious following fertility treatment and therefore more likely to report problems.The quality of most of the studies was high and they have adjusted for most important confounders of age and parity.- Some authors excluded pregnancies resulting from ovulation induction whereas others were not able to identify them from all non-IVF/ICSI conceptions.- The review cannot determine whether the increased risk is due to the inherent infertility itself or the process of ovarian stimulation and/or embryo culture.Qin et al, 2015 [22]Meta-analysis of 39 cohort studies- No evidence of publication bias among studies of ART and risk of adverse outcomes.- All the included original studies used a cohort study design, which minimizes recall and selection biases.- Some included studies have considered pregnancies arising after OI and IUI to be in the spontaneously generated category.- A number of the outcomes, especially for pregnancy-related complications, relied on between 1 and 8 of the 39 total studies.- The study population consisted of monochorionic and dichorionic twins, and monochorionic twins are known to be at high risk than dichorionic twins.- Residual confounding is a concern, although restricting analysis to studies that have matched or adjusted confounding factors did not materially alter the combined risk estimate.Qin et al, 2016 [23]Meta-analysis of 15 cohort studiesNo evidence of publication bias.26.7 % of the studies did not adjust and/or match any factorswhen estimating the effect of ART on obstetric outcomes indichorionic twin pregnancies.- More than half of the included studies had a small sample size.- Most of included studies belonged to retrospective cohort design.- There was substantial heterogeneity among studies for association between ART and obstetric risks in dichorionictwin pregnancies.- A number of the outcomes, especially for maternal complications, relied on between 2 and 7 of the 15 total studies.Pinborg et al, 2013 [9]Meta-analysis of 3 studies (for the considered outcome: PTB in SET vs. DET)Subfertility per se is a bias and it cannot be p...…”

Failure of fertility therapy and subsequent adverse cardiovascular events

“…1 Repeated cycles are often recommended, with mixed success and possible short-term metabolic risks. [2][3][4][5][6] However, few data are available on the long-term health effects of fertility therapy, particularly following unsuccessful treatment. 7 Failure of fertility therapy may be an early indicator of future cardiovascular risk by acting as a unique cardiometabolic stress test.…”