Live birth and perinatal outcomes following stimulated and unstimulated IVF: analysis of over two decades of a nationwide data

Abstract

Study question: Does ovarian stimulation affect perinatal outcomes of preterm birth (PTB) and low birth weight (LBW) following IVF treatment.

Summary answer: Despite no significant differences in the risks of PTB and LBW between stimulated and unstimulated IVF in the present study, the study cannot exclude the effect of ovarian stimulation on the perinatal outcomes following IVF.

What is already known: Pregnancies resulting from assisted reproductive treatments (ART) are associated with a higher risk of pregnancy complications compared to spontaneously conceived pregnancies attributed to the underlying infertility and the in vitro fertilization techniques. It is of interest to determine the effect size of ovarian stimulation use in achieving a live birth and whether ovarian stimulation that is routinely used in IVF, affects perinatal outcomes of birth weight and gestational age at delivery compared to unstimulated IVF.

Study design, size, duration: Anonymous data were obtained from the Human Fertilisation and Embryology Authority (HFEA), the statutory regulator of ART in the UK. The HFEA has collected data prospectively on all ART performed in the UK since 1991. Data from 1991 to 2011 comprising a total of 591 003 fresh IVF ± ICSI cycles involving 584 835 stimulated IVF cycles and 6168 unstimulated IVF cycles were analyzed.

Participants/materials, setting, methods: Data on all women undergoing either stimulated or unstimulated fresh IVF ± ICSI cycles during the period from 1991 to 2011 were analyzed to compare live birth rates, singleton live birth rates, perinatal outcomes of PTB, early PTB (<32 weeks), LBW and very LBW (<1500 grams) among singleton live births. Adjusted logistic regression was performed for each perinatal outcome for confounding factors: female age, period of treatment, cause of infertility, number of previous IVF cycles and previous live birth.

Main results and the role of chance: Analysis of the large nationwide data demonstrated 3.5 times (95% confidence interval (CI): 3.1-3.9) as many unstimulated IVF cycles being required to achieve one live birth compared to stimulated IVF and 2.9 times (95% CI: 2.6-3.2) as many unstimulated IVF cycles being required to achieve one singleton live birth compared to stimulated IVF. There was no significant difference in the unadjusted odds for PTB (odds ratio (OR) 1.27, 95% CI: 0.80-2.00) and LBW (OR 1.48, 95% CI: 0.90-2.42) between stimulated and unstimulated IVF cycles. There was no significant difference in the risk of the adverse perinatal outcomes after adjusting for potential confounders; PTB (adjusted odds ratio (aOR) 1.43, 95% CI: 0.91-2.26) and LBW (aOR 1.58, 95% CI: 0.96-2.58).

Limitations, reasons for caution: Although the analysis was adjusted for a number of important confounders, the dataset had no information on smoking, body mass index (BMI) and the medical history of women during pregnancy to allow adjustment. Anonymized nature of the dataset did not make it permissible to analyse one cycle per woman. Given the smaller number of perinatal events with unstimulated IVF, a larger study is needed to investigate further.

Wider implications of the findings: Analysis of this large dataset demonstrates that ovarian stimulation has a vital role in maximizing efficacy of IVF. Although there were no significant differences for PTB and LBW following stimulated compared to unstimulated IVF, the CIs were wide enough to include possible clinically important effects.

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

Keywords: live birth; low birth weight; preterm birth; stimulated IVF; unstimulated IVF.