Predicting Live Birth, Preterm Delivery, and Low Birth Weight in Infants Born from In Vitro Fertilisation: A Prospective Study of 144,018 Treatment Cycles

Abstract

Using the HFEA database of all 144,018 live births in all IVF cycles in the UK between 2003 and 2007, Scott Nelson and Debbie Lawlor show that couple- and treatment-specific factors can be used to help predict successful outcome following IVF.

Abstract

Background

The extent to which baseline couple characteristics affect the probability of live birth and adverse perinatal outcomes after assisted conception is unknown.

Methods and Findings

We utilised the Human Fertilisation and Embryology Authority database to examine the predictors of live birth in all in vitro fertilisation (IVF) cycles undertaken in the UK between 2003 and 2007 ( n = 144,018). We examined the potential clinical utility of a validated model that pre-dated the introduction of intracytoplasmic sperm injection (ICSI) as compared to a novel model. For those treatment cycles that resulted in a live singleton birth ( n = 24,226), we determined the associates of potential risk factors with preterm birth, low birth weight, and macrosomia. The overall rate of at least one live birth was 23.4 per 100 cycles (95% confidence interval [CI] 23.2–23.7). In multivariable models the odds of at least one live birth decreased with increasing maternal age, increasing duration of infertility, a greater number of previously unsuccessful IVF treatments, use of own oocytes, necessity for a second or third treatment cycle, or if it was not unexplained infertility. The association of own versus donor oocyte with reduced odds of live birth strengthened with increasing age of the mother. A previous IVF live birth increased the odds of future success (OR 1.58, 95% CI 1.46–1.71) more than that of a previous spontaneous live birth (OR 1.19, 95% CI 0.99–1.24); p-value for difference in estimate <0.001. Use of ICSI increased the odds of live birth, and male causes of infertility were associated with reduced odds of live birth only in couples who had not received ICSI. Prediction of live birth was feasible with moderate discrimination and excellent calibration; calibration was markedly improved in the novel compared to the established model. Preterm birth and low birth weight were increased if oocyte donation was required and ICSI was not used. Risk of macrosomia increased with advancing maternal age and a history of previous live births. Infertility due to cervical problems was associated with increased odds of all three outcomes—preterm birth, low birth weight, and macrosomia.

Conclusions

Pending external validation, our results show that couple- and treatment-specific factors can be used to provide infertile couples with an accurate assessment of whether they have low or high risk of a successful outcome following IVF.

Please see later in the article for the Editors' Summary

Editors' Summary

Background

Worldwide, more than 10% of couples are infertile. Sometimes there is no obvious reason for a couple's inability to have children but, for many couples, problems with their eggs or sperm prevent “fertilization”—the union of an egg and a sperm that leads, eventually, to the birth of a baby. Until recently, little could be done to help infertile couples. Then, on the 25 July 1978, the world's first “test-tube baby” was born. Since then, 4 million babies have been born through in vitro fertilization (IVF). In IVF, mature eggs are collected from the woman (or from an egg donor if the woman cannot make her own eggs) after a course of special hormones, and they are mixed in a dish with her partner's sperm. If her partner has a low sperm count or abnormal sperm, a single sperm can be injected directly into the egg in a procedure called intracytoplasmic sperm injection (ICSI), which became widely available in the mid 1990s, or sperm from a donor can be used. Finally, a number (depending on the country) of embryos (eggs that have begun to divide and develop) are put back into the woman where, hopefully, they will establish a successful pregnancy.

Why Was This Study Done?

Not every attempt at IVF is successful. In the US and the UK, IVF is successful in about a third of women under 35 years old but in only 5%–10% of women over the age of 40. It would be useful to have a way to predict the likelihood of a live birth after IVF for individual couples. Such a “prediction model” would facilitate patient counseling, clinical decision making, and the allocation of IVF resources. In this study, the researchers use information on IVF cycles collected by the Human Fertilisation and Embryology Authority (HFEA), which regulates IVF in the UK, to assess the extent to which the characteristics of infertile couples and the treatment they receive can be used to predict live birth after IVF. They also use these data to identify which factors are associated with preterm delivery, low birthweight, and macrosomia (the birth of an unusually large baby), three undesirable birth characteristics.

What Did the Researchers Do and Find?

Between 2003 and 2007, 163,425 IVF cycles were completed in the UK, 23.4% of which resulted in at least one live birth. The researchers used the data collected by the HFEA on 144,018 of these cycles (the other cycles had missing data) to develop a multivariable logistic regression prediction model (a type of statistical model) for the outcome of IVF. According to this model, a decreased chance of at least one live birth was associated with several factors including increasing maternal age, increasing duration of infertility, and the use of the woman's own oocytes. By contrast, a previous IVF live birth and the use of ICSI were associated with increased chances of success. Importantly, compared with an established multivariable prediction model, which was developed before the introduction of ICSI, the researchers' new prediction model predicted the chance of a live birth following IVF with greater accuracy. Finally, the researchers report that the chances of preterm and low birthweight after IVF were increased if donor eggs were required and ICSI was not used, that an increased risk of macrosomia was associated with increasing maternal age and with a history of previous live births, and that all three undesirable birth characteristics were associated with infertility due to cervical problems.

What Do These Findings Mean?

These findings indicate that couple- and treatment-specific factors can be used to provide infertile couples with an accurate assessment of whether they have a low or high chance of a successful outcome following IVF. The prediction model developed here provides a more accurate assessment of likely outcomes after IVF than a previously established model. Furthermore, because the new model considers the effect of ICSI on outcomes, it should be more useful in contemporary populations than the established model, which does not consider ICSI. However, before this new prediction model is used to guide clinical decisions and to counsel patients, it needs to be validated using independent IVF data. To facilitate the external validation of their model, the researchers are currently generating a free web-based prediction tool and iPhone application (IVFpredict).

Additional Information

Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000386.

• The Human Fertilisation and Embryology Authority provides information on IVF and IVF statistics for the UK

• The UK National Health Service Choices website provides information for patients on infertility and on IVF

• The American Pregnancy Association has information for patients on infertility and on IVF

• MedlinePlus has links to further resources on infertility and IVF (in English and Spanish)

• The history of the development of IVF is described on the Nobel Prize website

• The prediction tool that was used in this study is at http://www.IVFpredict.com