Perinatal outcomes in 6338 singletons born after intrauterine insemination in Denmark 2007 to 2012 The influence of ovarian stimulation

Treatment with clomiphene citrate is associated with an increased risk of small for gestational age in children born after intrauterine insemination, whereas ovarian stimulation with follicle-stimulating hormone did not seem to increase the risk of adverse perinatal outcomes.

Sara Sofia Malchau, M.D., Anne Loft, M.D., Anna-Karina A. Henningsen, M.D., Anders N. Andersen, M.D. D.M.Sci., Anja Pinborg, M.D., D.M.Sci.

Volume 102, Issue 4, Pages 1110-1116


To study perinatal outcomes in singletons born after intrauterine insemination (IUI) compared with children born after in vitro fertilization (IVF), intracytoplasmic sperm injection, and spontaneous conception (SC), and to assess predictors of poor outcome in singletons born after IUI, exploring the effect of ovarian stimulation.

National cohort study, 2007–2012.

Danish national registries.

Four thousand two hundred twenty-eight singletons born after insemination with partner semen (IUI-H) and 1,881 singletons born after insemination with donor semen.


Main Outcome Measure(s):
Preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA).

Children born after IUI-H had higher risks of PTB, LBW, and SGA vs. SC singletons (adjusted odds ratios [aOR] 1.3; 95% confidence interval (CI), 1.1–1.5; 1.4; 95% CI, 1.2–1.7; and 1.4; 95% CI, 1.2–1.6), respectively. Compared with IVF, risk of SGA was similar, but risks of PTB and LBW were lower (aOR 0.6; 95% CI, 0.5–0.8; and 0.8; 95% CI, 0.6–0.9). Compared with intracytoplasmic sperm injection, no differences were found. For children born after IUI with donor semen, results were similar to those for IUI-H. Risks of LBW and SGA were higher in IUI singletons born after ovarian stimulation with clomiphene citrate, compared with natural-cycle IUI (aOR 1.5; 95% CI, 1.1–2.1 and 1.6; 95% CI, 1.1–2.4). Treatment with follicle-stimulating hormone vs. natural-cycle IUI did not seem to affect perinatal outcomes.

Singletons born after IUI had higher risk of adverse perinatal outcomes compared with SC children, similar to ICSI, but favorable outcomes compared with IVF. Stimulation with clomiphene citrate was associated with higher risk of SGA compared with natural-cycle IUI, but follicle-stimulating hormone treatment did not seem to be associated with adverse outcomes.

  • Reshef Tal

    Thank you for this very interesting and large study. I have several questions/comments
    for the authors. The authors show that the IUI groups (both donor and partner
    semen) had significantly higher rates of preterm birth and low birth weight
    infants as compared to spontaneously conceived pregnancies. I find it
    interesting that the rates of hypertensive disorders were 2- fold higher in IUI
    women compared to spontaneous pregnancies (7.4% vs. 3.7%) which was significant.
    While the authors adjusted the data for various factors in their odds ratio analysis,
    it appears that they did not adjust for hypertensive disorders. Do the authors
    think that preeclampsia may be contributing to the higher preterm birth and low
    birth weight in the IUI population? Since IUI is a common treatment for PCOS
    and PCOS is associated with preeclampsia and pregnancy complications, it would
    also be important to know the proportion of PCOS women in the IUI vs. spontaneous
    conception group, and if these are significantly different would suggest
    excluding PCOS women to see if differences still remain. Also, I was quite
    surprised to see the relatively low preterm birth rate of the study population (being
    as low as 3.1%) as preterm birth is generally quoted at 10-12% of pregnant
    women. Do the authors have an explanation for this?

  • Shvetha Zarek

    It is interesting that children born after ICSI did not demonstrate any differences in preterm birth, low birth weight and small for gestational age compared to children born after IUI with partner semen, but differences were seen with IVF. In addition, children born after IUI with donor semen had similar risk compared to children born after IUI with partner semen. Both these observations suggest that female more than male infertility influences birth outcomes. Thank you for an interesting epidemiological study.

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