Simonsen, S. E., Baksh, L., & Stanford, J. B. (2016). Fertility treatments and adverse perinatal outcomes in a population-based sampling of births in Florida, Maryland, and Utah: a cross-sectional study. BJOG : an International Journal of Obstetrics and Gynaecology, 123(5), 718-729. https://doi.org/10.1111/1471-0528.13510
Simonsen SE, Baksh L, Stanford JB. Fertility treatments and adverse perinatal outcomes in a population-based sampling of births in Florida, Maryland, and Utah: a cross-sectional study. BJOG. 2016;123(5):718-729. doi:10.1111/1471-0528.13510
Simonsen, S. E., et al. "Fertility treatments and adverse perinatal outcomes in a population-based sampling of births in Florida, Maryland, and Utah: a cross-sectional study." BJOG : an International Journal of Obstetrics and Gynaecology, vol. 123, no. 5, 2016, pp. 718-729.
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Fertility treatment preterm risk is largely attributable to multiples
Fertility treatment is linked to preterm birth and low birthweight largely through multiple births. A survey of 21 803 mothers in Florida, Maryland, and Utah, 2004 to 2008, found about 33 out of 100 ART births were multiples, against about 1 out of 100 births without treatment.
Multiple births: Births without fertility treatment, 1.2 in 100; Births after ART, 33.2 in 100. Source: Simonsen SE et al., 2015, PMID 26148540.Study at a glance, cross-sectional survey of 21 803 mothers: Fertility treatment preterm risk is largely attributable to multiples. Source: Simonsen SE et al., 2015, PMID 26148540.
Key Findings
Singleton births after ART had higher odds of preterm birth (odds ratio 3.28, interval 1.74 to 6.20) and low birthweight (odds ratio 2.91, interval 1.99 to 4.26) than births without fertility treatment.
Counting all births, ART had higher odds of preterm birth (odds ratio 6.21, interval 4.21 to 9.16) and low birthweight (odds ratio 6.51, interval 4.85 to 8.73) than births without fertility treatment.
Against women with trouble getting pregnant who conceived without treatment, ART was associated with preterm birth in all births (OR 3.21). Among singletons, no significant association appeared.
Multiple gestation occurred in 33.2% of ART births (95% CI 25.6, 40.8) and 1.2% of births without treatment (95% CI 0.9, 1.5).
Counting all births, IUI (OR 2.10; 95% CI 1.24, 3.56) and ovulation stimulation alone (OR 1.40; 95% CI 1.01, 1.94) were also associated with preterm birth.
Interpretation
The study is a cross-sectional survey, a one-time snapshot, so it shows associations and cannot show cause. Mothers reported their own treatment in the month of conception. The data could not identify embryo number, frozen transfers, or donor eggs or sperm. The authors assumed women who reported no specific treatment had conceived without it, and had no information on how long couples had been trying. Only women with live births were included, and comparisons covered women trying to get pregnant. The authors judged the group labeled "other" too mixed to support conclusions about any single treatment.
RRM Context
Restorative reproductive medicine works on the cause of trouble getting pregnant. In this survey, women who reported past treatment but none in the month of conception had modestly raised odds of these outcomes against women who used no treatment. Only very low birthweight reached significance, with an odds ratio of 1.90 (95% CI 1.25, 2.89). The authors say the data support future investigation of treatments that seek to restore normal reproductive function.
Our editorial summary of this paper, not the article's abstract.
Abstract
Objective
To investigate perinatal outcomes associated with fertility treatments, including assisted reproductive technology (ART), intrauterine insemination with ovulation stimulation (IUI), and ovulation stimulation alone (OS).
Design
Population-representative cross-sectional survey of women with live births, 2004-2008.
Setting
Florida, Maryland, and Utah, USA.
Sample
21 803 women, weighted to represent 1 022 597 women.
Methods
Survey and birth certificate data were analysed with logistic regression models adjusted for age, education, race, income, and parity, using separate models for singletons and all births. We used two referent groups: (1) women who never used fertility treatment and (2) subfertile women conceiving without treatment.
Main Outcome Measures
Preterm birth (<37 weeks), very preterm birth (<34 weeks), low birthweight (<2500 g), and very low birthweight (<1500 g).
Results
Referent group 1: In singletons, ART was associated with preterm birth (OR 3.28; 95% CI 1.74, 6.20) and low birthweight (OR 2.91; 95% CI 1.99, 4.26). OS was also associated with low birthweight (OR 1.62; 95% CI 1.19, 2.19). Including all births, treatment was associated with preterm birth and low birthweight: ART (OR 6.21; 95% CI 4.21, 9.16 and OR 6.51; 95% CI 4.85, 8.73); IUI (OR 2.10; 95% CI 1.24, 3.56 and OR 2.41; 95% CI 1.54, 3.76); OS (OR 1.40; 95% CI 1.01, 1.94 and OR 2.10; 95% CI 1.60, 2.75), respectively. Referent group 2: ART was associated with both outcomes in all births, but not singletons.
Conclusions
Preterm birth and low birthweight associated with fertility treatments are largely attributable to multiple gestation, but are also related to underlying subfertility.
Tweetable Abstract
Preterm birth is associated with subfertility, and with fertility treatments through multiple gestation.
