P-790 Mode of conception and pregnancy outcomes: systematic review and meta-analysis of 110 studies and 33,655,021 singleton pregnancies
Authors: Beebeejaun Y , Baird F , Showell M , Sunkara S 
Published: June 2022

Study question

Does mode of conception such as in-vitro fertilisation (IVF), ovulation induction (OI), intra-uterine insemination (IUI) affect singleton pregnancy outcomes when compared to spontaneous conception (SC)?

Summary answer

Singleton pregnancies resulting from OI, IUI, IVF are associated with higher risks of adverse pregnancy outcomes compared to spontaneous pregnancies.

What is known already

Several meta-analysis have shown singleton pregnancies resulting from IVF have adverse pregnancy outcomes However, these studies had much smaller sample size and did not compare OI or IUI to SC. Additionally, when matched studies were analysed, the pooled events used were not adjust for medical conditions such as polycystic ovaries (PCO) and chronic hypertension which predispose patients to gestational diabetes(GDM) and pre-eclampsia (PET).he lack of consensus on how PET and GDM was defined was also a cause of bias. Our study is the largest meta-analysis to date and aims to provide clinician with the latest evidence when offering fertility treatment.

Study design, size, duration

Literature search in MEDLINE, COCHRANE Library, and Scopus was performed, up to November 2021. Randomised controlled trials (RCTs), non-randomised studies, cohort and case control studies, reporting on any association between pregnancy outcome, such as pre-eclampsia (PET), gestational diabetes mellitus (GDM), preterm birth, (&lt;37 weeks (TB), very preterm birth , (&lt;32 weeks (vVPTB), low birthweight (&lt;2500g,LBW), very low birth weight (&lt;1500g,VLBW) and small gestational age (SGA) in relation to mode of conception were included.

Participants/materials, setting, methods

110 studies consisting of 31 cohort studies and 79 case control were included comprising a total of 32,463,058spontaneous singleton conception compared to 1,191,963 singleton pregnancies following OI, IUI and IVF treatment .Matching criteria used for adjustment were also identified For PET and GDM, only studies which defined the condition according to international agreed consensus were included Any inconsistency between studies was quantified through Higgins’ Chi-square (Chi2) and I-squared (I2) using statistical software R.

Main results and the role of chance

Singleton pregnancies following, OI, IUI, or IVF had a higher odds of PET compared to SC (odds ratio [OR]1.95,, 95% confidence interval [CI]1.61-2.31; I2=97%), OR 1.53, 95%CI 1.36 -1.71,, I2=84% and OR1.62, 95%CI 0.94-2.78, I2=11%).respectively. For GDM, pregnancies following, OI, IUI, or IVF had a higher odds compared to SC (OR1.59, 95%CI 1.59 -1.71, I2=83%, OR 1.62, 95%CI 0.94-2.78, I2=11% and OR1.72, 95% CI 1.49–1.98; I2=13%). Higher odds of TB and vPTB were seen in pregnancies following OI and IVF compared to SC (PTB: OR1.80, 95% CI 1.76–1.85; I2=94% and , (OR 1.47, 95% CI 1.22-1.77 I2=66% and vPTB OR 2.92, 95% CI 2.76-3.09; I2=91%). Only one study reported PTB when comparing IUI to SC (OR 1.88, 95% CI 1.40-2.53) and comparing vPTB in OI vs SC (OR 1.73 95% CI 0.71-4.18). Singleton pregnancies following, OI or IVF had a higher odds of LBW and vLBW compared to SC (OR1.98, 95% CI 1.93–2.04; I2=96%),OR1.72, 95% CI 1.49–1.98 I2=13% and OR4.57, 95% CI 4.34–4.81; I2=98% and OR2.32, 95% CI 1.60–3.37; I2=56% respectively. The rate of SGA was comparable in IVF (OR 0.91, 95% CI 0.90–0.93; I2=99%), OI (OR 0.96, 95% CI 0.95-0.97; I2=100%) and IUI (RR 0.92, 95% CI 0.90–0.94; I2=31%).

Limitations, reasons for caution

In cases of PE and GDM, published definitions differed in various studies and there was limited information given past medical history which increase the risk of such conditions. This made it impossible to separate the baseline confounders which may increase the risk of PE and consequently PTB, SGA and LBW.

Wider implications of the findings

Our meta-analysis confirmed that IVF/ICSI pregnancies are at higher odds of adverse pregnancy outcomes. This is the largest systematic review to date analysing pregnancy outcomes and mode of conception comparing OI, IUI and IVF respectively. It provides the latest evidence possible for clinicians to choose the safest fertility treatment,

Trial registration number

Not applicable