IVF and increased risk for preeclampsia revisited: a meta-analysis

Abstract

ObjectiveIn vitro culture of embryos could produce subtle changes, altering trophoblast invasion. Associated poor placentation can, in turn, lead to preeclampsia. We investigated if pregnancies resulting from in vitro fertilization (IVF) are at increased risk of developing preeclampsia (PE) or pregnancy induced hypertension (PIH) compared to spontaneously conceived pregnancies and other assisted reproductive technologies (ART).DesignMeta-analysis of published papers.Materials and MethodsElectronic searches (MEDLINE, PUBMED, OVID) identified studies from 1995-2011, using search terms in vitro fertilization, assisted reproductive technology, hypertensive disorders, preeclampsia, donor oocyte and intracytoplasmic sperm injection. Types of IVF included standard IVF, intracytoplasmic sperm injection and IVF with donor oocyte. Control groups included spontaneous pregnancies, as well as ART with ovulation induction and intrauterine insemination. Other factors such as age, multiple gestations, and parity were abstracted. Primary outcome was the rate of PE/PIH. Analyses were performed using Fisher's exact tests; number of patients in each group was pooled for weighted analysis. Meta-analysis was performed by odds ratios (OR) with forest plots.ResultsOf 43 investigations, only 18 met study criteria. PE/PIH was significantly more common among all IVF groups combined vs controls (92% vs 8%; P=0.04) with a stronger association when weighted by group size (88% vs 12%; P<0.0001). Of 18 studies, only 6 had enough detail for meta-analysis. PE/PIH was significantly higher after IVF than in control groups (OR = 1.41; 95%CI = 1.33-1.50; P<0.0001).ConclusionThis meta-analysis supports the hypothesis that exposure of a preimplantation embryo to in vitro culture predisposes the conceptus to poor trophoblast differentiation and placental insufficiency, leading to an increased risk of preeclampsia. ObjectiveIn vitro culture of embryos could produce subtle changes, altering trophoblast invasion. Associated poor placentation can, in turn, lead to preeclampsia. We investigated if pregnancies resulting from in vitro fertilization (IVF) are at increased risk of developing preeclampsia (PE) or pregnancy induced hypertension (PIH) compared to spontaneously conceived pregnancies and other assisted reproductive technologies (ART). In vitro culture of embryos could produce subtle changes, altering trophoblast invasion. Associated poor placentation can, in turn, lead to preeclampsia. We investigated if pregnancies resulting from in vitro fertilization (IVF) are at increased risk of developing preeclampsia (PE) or pregnancy induced hypertension (PIH) compared to spontaneously conceived pregnancies and other assisted reproductive technologies (ART). DesignMeta-analysis of published papers. Meta-analysis of published papers. Materials and MethodsElectronic searches (MEDLINE, PUBMED, OVID) identified studies from 1995-2011, using search terms in vitro fertilization, assisted reproductive technology, hypertensive disorders, preeclampsia, donor oocyte and intracytoplasmic sperm injection. Types of IVF included standard IVF, intracytoplasmic sperm injection and IVF with donor oocyte. Control groups included spontaneous pregnancies, as well as ART with ovulation induction and intrauterine insemination. Other factors such as age, multiple gestations, and parity were abstracted. Primary outcome was the rate of PE/PIH. Analyses were performed using Fisher's exact tests; number of patients in each group was pooled for weighted analysis. Meta-analysis was performed by odds ratios (OR) with forest plots. Electronic searches (MEDLINE, PUBMED, OVID) identified studies from 1995-2011, using search terms in vitro fertilization, assisted reproductive technology, hypertensive disorders, preeclampsia, donor oocyte and intracytoplasmic sperm injection. Types of IVF included standard IVF, intracytoplasmic sperm injection and IVF with donor oocyte. Control groups included spontaneous pregnancies, as well as ART with ovulation induction and intrauterine insemination. Other factors such as age, multiple gestations, and parity were abstracted. Primary outcome was the rate of PE/PIH. Analyses were performed using Fisher's exact tests; number of patients in each group was pooled for weighted analysis. Meta-analysis was performed by odds ratios (OR) with forest plots. ResultsOf 43 investigations, only 18 met study criteria. PE/PIH was significantly more common among all IVF groups combined vs controls (92% vs 8%; P=0.04) with a stronger association when weighted by group size (88% vs 12%; P<0.0001). Of 18 studies, only 6 had enough detail for meta-analysis. PE/PIH was significantly higher after IVF than in control groups (OR = 1.41; 95%CI = 1.33-1.50; P<0.0001). Of 43 investigations, only 18 met study criteria. PE/PIH was significantly more common among all IVF groups combined vs controls (92% vs 8%; P=0.04) with a stronger association when weighted by group size (88% vs 12%; P<0.0001). Of 18 studies, only 6 had enough detail for meta-analysis. PE/PIH was significantly higher after IVF than in control groups (OR = 1.41; 95%CI = 1.33-1.50; P<0.0001). ConclusionThis meta-analysis supports the hypothesis that exposure of a preimplantation embryo to in vitro culture predisposes the conceptus to poor trophoblast differentiation and placental insufficiency, leading to an increased risk of preeclampsia. This meta-analysis supports the hypothesis that exposure of a preimplantation embryo to in vitro culture predisposes the conceptus to poor trophoblast differentiation and placental insufficiency, leading to an increased risk of preeclampsia.