Increased time-to-pregnancy and first trimester Down's syndrome screening.

Background: Time-to-pregnancy (TTP) is a clinical tool used to measure uterine receptivity and a couples' fertility in spontaneously conceived pregnancies. The objective of this study was to examine the effects of TTP on first trimester Down's syndrome (DS) markers in spontaneous, chromosomally normal pregnancies and to compare the results to those in IVF pregnancies.

Methods: A case-control study was conducted amongst patients attending a university hospital in Finland. During 2005-2007 data on pregnant women in Kuopio, with singleton pregnancies, routinely collected by the Department of Obstetrics and Gynaecology of Kuopio University Hospital and Eastern Finland Laboratory Centre were compiled. The data comprised information gathered in first trimester DS screening [age of the mother, serum hCG free beta subunit (fbeta-hCG) and pregnancy-associated plasma protein A (S-PAPP-A) levels and the nuchal translucency (NT) of the fetus], body mass index, method of conception [spontaneous or in vitro fertilization (IVF)], TTP (in spontaneous pregnancies), maternal chronic diseases, smoking habits of the mother, outcome of the pregnancy and prior pregnancy complications. Spontaneous pregnancies were classified into three groups by TTP: 0-12 months (the reference group, N = 1164), 13-24 months (N = 112) and > or = 25 months (N = 70). Screening data from IVF pregnancies (N = 39) were collected for comparison. The size of the total study population was 1385.

Results: The median/geometric mean multiple of median (MOM) of S-PAPP-A was significantly lower (P < 0.01) in women with a TTP over 25 months (0.89/0.83 MOM) and in the IVF group (0.95/0.84 MOM) compared with the reference group (1.01/1.03 MOM). However, first trimester S-fbeta-hCG and NT MOMs were not statistically different between the study groups. Consequently, the proportion of DS screening positives was significantly higher in women with TTP > or = 25 months (12.9 versus 2.1%), but not in the IVF group (2.6%).

Conclusions: A TTP of over 2 years altered the levels of DS screening serum markers to levels similar to those observed in IVF pregnancies, with a decrease in PAPP-A levels compared with the reference group. These results raise the possibility that such changes could be related to subfertility rather than to the use of assisted reproductive technology.