Assessment of separate contributions to perinatal mortality of infertility history and treatment: a case-control analysis

Lancet. 1999 May 22;353(9166):1746-9. doi: 10.1016/S0140-6736(98)08500-6.


Background: Few studies have described the perinatal risks associated with infertility, other than for infertility treated by in-vitro fertilisation or gamete intrafallopian transfer. The aim of this analysis was to estimate the risks of perinatal death associated with treated and untreated infertility.

Methods: A population-based case-control study of perinatal deaths was carried out in Leicestershire Health District over the period 1990-94, during which 60,922 babies were delivered. Of these, 567 perinatal deaths were associated with 542 women. 972 mothers were randomly selected as controls. Medical, obstetric, and social data were collected for cases and controls from the medical notes and interviews with the women. The relative risks of perinatal death associated with treated and untreated infertility before the index pregnancy were estimated as odds ratios by means of unconditional logistic regression analysis.

Findings: 65 (10%) of cases and 34 (3.5%) of the controls had infertility before the index pregnancy. History of infertility in the index pregnancy, irrespective of treatment, increased the risk of perinatal death (odds ratio 2.9 [95% CI 1.8-4.5]). The population attributable risk fraction for perinatal death related to infertility was 6.2% (3.4-9.0). 45 (54%) of the deaths, even in the untreated group, were associated with immaturity. Compared with women without infertility, women with untreated infertility were at increased risk of perinatal death (3.3 [1.6-6.8]). The risk of perinatal death associated with multiple births did not explain this finding. Similarly, treated infertility also increased the risk of perinatal death (2.7 [1.5-4.7]); the risks associated with multiple births explained some, but not all, of this excess. In Leicestershire, the overall underlying risk of a mother experiencing at least one perinatal death over the study was 9.0 per 1000 women. For women who experience infertility, this risk increases by about 18 per 1000 (6-30).

Interpretation: Counselling for women before any form of infertility treatment should include discussion of the risks of perinatal death. Our results would benefit from confirmation. However, we advocate that at antenatal booking a history of infertility, irrespective of treatment, should be sought, because these women have a significantly increased risk of perinatal death, particularly associated with prematurity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Confounding Factors, Epidemiologic
  • England / epidemiology
  • Female
  • Fertilization in Vitro / adverse effects*
  • Gamete Intrafallopian Transfer / adverse effects*
  • Humans
  • Infant Mortality*
  • Infant, Newborn
  • Infertility, Female / therapy*
  • Logistic Models
  • Ovulation Induction / adverse effects
  • Pregnancy
  • Pregnancy Outcome
  • Risk Factors