Increased risk of preterm birth and low birthweight with very high number of oocytes following IVF: an analysis of 65 868 singleton live birth outcomes

Study question: Is there a relation between the number of oocytes retrieved following ovarian stimulation and obstetric outcomes of preterm birth (PTB) and low birthweight (LBW) following IVF treatment?

Summary answer: There is an increased risk of PTB (<37 weeks gestation) and LBW (<2500 g) following IVF in women with a high number (>20) of oocytes retrieved.

What is known already: Pregnancies resulting from assisted reproductive treatments (ART) are associated with a higher risk of pregnancy complications compared with spontaneously conceived pregnancies. Whether ovarian ageing in women with poor ovarian response is associated with an increased risk of adverse obstetric outcomes is debated. It is also unclear if an excessive response and high egg numbers following ovarian stimulation have an association with adverse obstetric outcomes.

Study design, size, duration: Observational study using anonymized data on all IVF cycles performed in the UK from August 1991 to June 2008. Data from 402 185 IVF cycles and 65 868 singleton live birth outcomes were analysed.

Participants/materials, setting, methods: Data on all women undergoing a stimulated fresh IVF cycle with at least one oocyte retrieved between 1991 and June 2008 were analysed for birth outcomes. Logistic regression analysis of the association between ovarian response (quantified as number of oocytes retrieved) and outcomes of PTB and LBW was performed.

Main results and the role of chance: There was a significantly higher risk of adverse obstetric outcomes of PTB and LBW among women with an excessive response (>20 oocytes) compared with women with a normal response (10-15 oocytes): adjusted odds ratio (OR) 1.15, 95% confidence interval (CI) 1.03-1.28 for PTB, adjusted OR 1.17, 95% CI 1.05-1.30 for LBW, respectively. There was no increased risk of the adverse outcomes among women with a poor ovarian response (≤3 oocytes) compared with women with a normal response: adjusted OR 0.88, 95% CI 0.76-1.01 for PTB, adjusted OR 0.92, 95% CI 0.79-1.06 for LBW, respectively.

Limitations, reasons for caution: Although the analysis was adjusted for a number of potential confounders, the dataset had no information on other important confounders such as smoking, BMI and the medical history of women during pregnancy. Furthermore, the dataset did not allow specific identification of women with PCOS and its anonymized nature did not make it permissible to analyse one cycle per woman.

Wider implications of the findings: Analysis of this large dataset suggests that a high oocyte number (>20) following IVF is associated with a higher risk of PTB and LBW. These findings lead to speculation whether ovarian dysfunction and/or an altered endometrial milieu resulting from supraphysiological steroid levels underlie the unfavourable outcomes and warrant further research. Ovarian stimulation regimens should optimize the number of oocytes retrieved to avoid the risk of adverse outcomes associated with very high numbers of oocytes.

Study funding/competing interests: No funding was obtained. There are no competing interests to declare.