Department of Obstetrics and Gynaecology, University of Aberdeen, Aberdeen Maternity Hospital, Aberdeen AB25 2ZD, UK
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Abstract |
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Key words: obstetric outcome/perinatal outcome/treatment-independent/treatment-related/unexplained infertility
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Introduction |
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A quarter of all infertile couples have unexplained infertility (Templeton and Penney, 1982). In comparison with other groups, these couples experience a relatively high spontaneous pregnancy rate (Templeton and Penney, 1982
; Collins et al., 1995
), but also face the prospect of treatment, which in the absence of a diagnosed cause is essentially empirical. These are important considerations which should be taken into account when deciding the timing and choice of treatment, especially if treatment has the potential to increase maternal and fetal risks.
We aimed to assess the obstetric risks associated with unexplained infertility and explore the factors responsible for them by comparing firstly, the outcome of pregnancy in couples with unexplained infertility with that in the general population and secondly, treatment-related and treatment-independent pregnancies. As many of these risks are associated with multiple pregnancies, these were excluded from our analysis. The presence of two large local databases [The Aberdeen Maternity and Neonatal Databank (AMND) and the Aberdeen Fertility Clinic database] and the presence of a relatively stable population in the north-east of Scotland allowed us to perform these comparisons. The AMND contains information on all obstetric and fertility related gynaecological events in women in a defined geographical area (Aberdeen City District) with a stable catchment population since 1951 (Samphier and Thompson, 1981). Stringent and consistent criteria, which are essential both for studies of secular change and for intergenerational studies, have been used for the coding of gestational length, birth weight, pregnancy complications and the classification of perinatal events. Since 1989 the Aberdeen Fertility Clinic database has collected information prospectively related to all couples referred to the Fertility Clinic and contains detailed case records of more than 4000 couples. Record linkage allows easy identification of complete reproductive histories of individuals as well as families.
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Materials and methods |
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Obstetric records of the women with unexplained infertility were identified from the AMND by using name and unit number. Data related to maternal and perinatal complications were obtained, and the results were then compared with the figures for the local obstetric population during the same period of time. The outcomes of spontaneous and treatment-related pregnancies were also compared. Only the first delivery that occurred after the onset of investigation was studied.
Multiple pregnancies were excluded from the analysis because they carry a higher risk of obstetric and perinatal complications in comparison with singleton pregnancies. As birth weight is not normally distributed at each week of gestation, birth weights were assessed using standardized birth weight score (SBW) which adjusts for parity, gestation and sex of the newborn (Campbell et al., 1993).
Statistics
Statistical analysis was carried out using the statistical package SPSS for windows (Statistical Package for Social Sciences). Student's t-test, the MannWhitney U-test, Fisher's exact test and 2 test were used where appropriate. Confidence intervals were calculated using the CIA programme (Wilson's method).
Logistic regression was used to calculate unadjusted and adjusted odds ratios where indicated.
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Results |
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The outcome of pregnancies in women with unexplained infertility is shown in Figure 1. The multiple pregnancy rate was 5.4% higher in the treatment group compared with the spontaneous pregnancy group (95% CI for difference = +2.8 to +9.7).
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Discussion |
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This is the largest descriptive study focusing on couples with unexplained infertility. Collection of data from both the Fertility Clinic database and the AMND was done prospectively, thus reducing recall bias. Standardized birthweight score (SBW) was preferred to crude birthweight in determining differences in birth weights of infants of the couples in the study.
Some difficulties were encountered during this study. In comparison with the general population, women with unexplained infertility are usually older and are less likely to have had previous deliveries. Multiple births are common and a significant proportion of women would have been exposed to assisted reproductive techniques. Under these conditions, identification of an appropriate matched control can be difficult (McFaul et al., 1993). We decided to use women who conceived spontaneously and delivered between 1989 and 1999 in Aberdeen as a comparison group and adjusted for differences in age and parity. Only data relating to singletons were analysed in order to avoid the possible confounding effects of multiple pregnancies.
We also made the assumption that the details of all women who were resident in Aberdeen and had a pregnancy outcome during the period of the study would be registered with the AMND. Although there is a possibility that a small number of women could have delivered elsewhere, the relative stability of the Aberdeen population which has an out-migration rate (including deaths) of about 3% (Hall et al., 1989), ensures that those delivering elsewhere constitute a small minority.
The literature surrounding obstetric outcome in couples with unexplained infertility is very limited. Most studies involve relatively small numbers of patients with limited follow-up (Sundstrom et al., 1997; Isaksson and Tiitinen, 1998
). The results of our study agree with some previous reports (Saunders et al., 1988
; Reubinoff et al., 1997
; Isaksson and Tiitinen, 1998
) which suggest that infertility treatment per se is not associated with a higher incidence of pre eclampsia, abruption and preterm deliveries. In contrast to previous reports (Tuck et al., 1988
; Li et al., 1991
), our study fails to confirm a link between these complications and advanced maternal age.
In comparison with the general population, there seemed to be a lower threshold for obstetric interventions including induction of labour and Caesarean sections in couples with unexplained infertility. Contrary to findings from previous studies (Reubinoff et al., 1997), fertility treatment did not seem to influence the rate of Caesarean sections. Overall, the lower threshold for obstetric interventions in these couples could be partly attributed to the anxiety around these pregnancies and the influence of a history of infertility on the clinician's decision making.
The results of our study indicate no increase in perinatal risks in couples with unexplained infertility. Adverse perinatal outcomes including stillbirth, low birth weight, neonatal unit admissions, and early and late neonatal deaths in women undergoing assisted reproduction treatment have been reported by various authors (Rizk et al., 1991; McFaul et al., 1993
). The comparable birth weights in the treatment-independent and treatment-related groups observed in our study concur with results of some studies (Frydman et al., 1986
; Hill et al., 1990
; Reubinoff et al., 1997
) but not with others (Rizk et al., 1991
; McFaul et al., 1993
; Olivennes et al., 1997
). The disparity of the results in the literature may be due to differences in statistical power, study design, choice of controls and the possible confounding effects of premature babies. For many of the rarer events of interest, especially perinatal mortality, a much larger number of patients is required to provide the statistical power necessary to draw any firm conclusions. In comparison with other published reports (Beral and Doyle, 1990
; Bergh et al., 1999
; SART registry, 1999
) the group of patients who underwent assisted reproduction treatment in our study was small.
Women with a history of unexplained infertility are perhaps more closely monitored than others and consequently have a higher pick-up rate of any potential problems. This may lead to an increased diagnosis of obstetric complications and a greater chance of surgical intervention. Traditionally, a higher complication rate in these women has been ascribed to increased maternal age and a higher proportion of multiple pregnancies. Our study shows that these risks persist even after adjusting for these factors. Apart from increasing the chance of multiple pregnancy, fertility treatment per se does not increase either the complication rate or the rate of intervention in these women. Although a lower threshold for intervention cannot be ruled out, women with unexplained infertility may be a genuine high risk group who would benefit from better counselling and additional care. More work is needed to explore the link between obstetric complications and unexplained infertility.
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Acknowledgements |
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Notes |
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References |
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Submitted on April 9, 2001; accepted on September 6, 2001.