The course of pregnancy and delivery and the use of maternal healthcare services after standard IVF in Northern Finland 1990–1995

Sari Koivurova1,2,6, Anna-Liisa Hartikainen1,2, Liisa Karinen1,2, Mika Gissler4, Elina Hemminki4, Hannu Martikainen2, Leena Tuomivaara3 and Marjo-Riitta Järvelin1,5

1 Department of Public Health Science and General Practice, University of Oulu, P.O.Box 5000, 90014 Oulu, 2 Department of Obstetrics and Gynecology, University Hospital of Oulu, P.O.Box 24, 90029 Oulu, 3 The Family Federation of Finland, Kiviharjuntie 11, 90220 Oulu, 4 National Research and Development Center for Welfare and Health, P.O.Box 220, 00531 Helsinki, Finland and 5 Department of Epidemiology and Public Health, Imperial College School of Medicine, London, UK


    Abstract
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
BACKGROUND: The objective of this study was to evaluate the course of pregnancy and delivery and the use of maternal healthcare after IVF. METHODS: This population-based cohort study included all women who had undergone IVF treatment in Northern Finland leading to delivery in 1990–1995 (n = 225) and control pregnancies derived from the Finnish Medical Birth Register (n = 671) matched for sex of the child, year of birth, area, maternal age, parity, social class and fetal plurality. The analyses were stratified by plurality. Outcome measures were pregnancy complications, mode of delivery, gestational length and the level of use of antenatal care. RESULTS: The results showed an increased risk for vaginal bleeding throughout pregnancy [relative risk (RR) 4.1, 95% confidence interval (CI) 2.5–6.7 for singletons; RR 6.9, 95% CI 2.5–19.2 for twins], threatened preterm birth (RR 1.8, 95% CI 1.1–2.9, singletons) and intrahepatic cholestasis of pregnancy (RR 3.8, 95% CI 1.0–15.0, singletons) in IVF pregnancies, as well as an increase in the use of specialized antenatal care. CONCLUSIONS: IVF pregnancies following standard, fresh ova IVF treatments are at greater risk of obstetric problems than spontaneously conceived pregnancies, and hence IVF mothers use more specialized antenatal care than others. The pregnancy complications after IVF are likely to be due to maternal characteristics regarding infertility and to a high incidence of multiple pregnancies.

Key words: delivery/healthcare services/IVF/pregnancy complications


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
Since the birth of the first IVF child in 1978 (Steptoe and Edwards, 1978Go), the IVF procedure has become a common treatment for infertile couples, enabling them to have children. Later, ICSI was developed to enhance the results of male infertility treatment. The wide use of assisted reproductive technology (ART) has raised questions as to whether these procedures have an effect on the outcome of pregnancy and the newborn.

There are certain maternal characteristics in the infertile population. Infertile women are more often older and nulliparous than others and have a more adverse pregnancy history (Gissler et al., 1995Go). It has been reported that there is more pregnancy-induced hypertension (PIH) (Tan et al., 1992Go; Tallo et al., 1995Go; Tanbo et al., 1995Go) and gestational diabetes mellitus (GDM) after IVF (Maman et al., 1998Go). It is well known that infertility treatments increase the number of multiple pregnancies, leading to preterm deliveries, low birth weight and small for gestational age newborns, which are regarded as the main reasons for adverse neonatal outcome (Friedler et al., 1992Go; Balen et al., 1993Go; Gissler et al., 1995Go; Bergh et al., 1999Go; Buitendijk, 1999Go). Furthermore, there is an increased risk for preterm delivery and low birth weight even in singleton IVF pregnancies (Wang et al., 1994Go; Tanbo et al., 1995Go; Verlaenen et al., 1995Go; Buitendijk, 1999Go). A few studies have also indicated that the Caesarean section rate is higher in IVF than in spontaneous pregnancies (Tan et al., 1992Go; Verlaenen et al., 1995Go; Reubinoff et al., 1997Go). According to a Finnish study, IVF mothers had significantly more antenatal care visits, they were more often hospitalized during pregnancy and had longer hospitalizations after delivery than others (Gissler et al., 1995Go). To date, there is no evidence that the IVF technology itself is the cause of these facts; rather, it seems that the maternal characteristics regarding infertility and the high incidence of multiple pregnancies have an impact on this matter (Olivennes et al., 1993Go; McElrath and Wise, 1997Go).

The aim of this population-based cohort study was to evaluate the effect of IVF technology on the course of pregnancy by comparing IVF pregnancies and deliveries with naturally conceived controls matched for maternal age, parity and social class. The selected matching criteria are known to associate both with infertility and pregnancy outcome (Sipilä et al., 1994Go). In order to evaluate the course of multiple IVF and naturally conceived pregnancies, an additional stratification was performed by the number of fetuses. Furthermore, we compared the use of maternal healthcare between the groups, on which there are few data in the literature. Based on the previous literature, our hypothesis was that IVF pregnancies carry an increased risk for pregnancy complications such as vaginal bleeding, preterm birth, pregnancy-induced hypertension and intrauterine growth restriction (IUGR), and that IVF mothers make more use of maternal healthcare than others.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
We carried out a cohort study, based on previously recorded data of conventional fresh ova IVF pregnancies (exposed, n = 225) leading to birth. The subjects were derived from registers at the IVF out-patient clinic in the University Hospital and the Infertility Clinic of the Family Federation of Finland in Oulu, covering all IVF treatments during 1990–1995 in Northern Finland, i.e. the provinces of Oulu and Lapland, which is by area about half of the country. In Finland, IVF treatments take place in all five university hospitals as well as in two central hospitals, and in the private sector. All livebirths and stillbirths after completion of week 22 of gestation or with a birth weight of >=500 g were regarded as births.

This study is part of an extensive project exploring the course of IVF pregnancies and the growth and development of IVF children. The control cohorts were randomly chosen from the Finnish Medical Birth Register (FMBR). The matching technique for mothers was based on the matching of IVF children and their controls, previously explained in detail (Koivurova et al., 2002Go). The number of unexposed mothers was dependent on the number of fetuses and children born after IVF. Firstly, for each IVF-born child, we selected two controls (that is, two mothers). This control group represented the general population in proportion of multiple births and was matched for sex of the child, year of child’s birth, area of residence (province), parity, maternal age and social class defined by occupation of the mother [upper white collar, lower white collar, blue collar, entrepreneurs (small business) and farmers, students, housewives and unknown].

Secondly, to evaluate the effect of IVF on the course of pregnancy and the newborn by multiplicity, we selected an additional control cohort (1:1), also matched for plurality, in order to have enough naturally conceived multiple control pregnancies/births and finally children. In the present analyses, we pooled all singleton and twin mothers together to have as high a power as possible, making sure that the matching criteria at group level applied, and conducted the analyses by plurality. That is why the matching proportions, 1:2 and 1:1, cannot directly be seen in the tables. In total, there were 671 control births for the analysis with appropriate data. Prestudy sample size calculations were based on the number of IVF children and their expected developmental outcomes in the long-term (Koivurova et al., 2002Go). The number of pregnancies in the present analyses indicated that we needed at least a 1.8 relative risk (RR) to detect a difference between the IVF and unexposed groups with a power of 0.80 at a 95% confidence level, assuming ~6–10% occurrence of main pregnancy complications in the unexposed population of this age range (e.g. preterm birth). This result also applies to mothers of singletons when the analyses are stratified by plurality. Among the mothers of twins, RR should be at least 2.8 to detect a statistically significant difference between the groups.

Data concerning pregnancy, delivery and the use of maternal healthcare services were collected from hospital records by a resident physician (S.K.). Outcome measures were maternal disorders during pregnancy and other pregnancy complications, mode of delivery, gestational age at birth, the number of antenatal care visits to healthcare centres and out-patient clinics, and length of hospitalizations during pregnancy and after delivery.

Threatened preterm birth was defined as uterine contractions with dilated or non-dilated cervix needing specialized care in hospital. PIH was defined as gestational hypertension or pre-eclampsia. The criteria for gestational hypertension were systolic blood pressure >=140 mmHg or elevation >=30 mmHg during pregnancy, and diastolic blood pressure >=90 mmHg or elevation >=15 mmHg during pregnancy. In addition, the diagnosis of pre-eclampsia required proteinuria >0.3 g/day with or without subjective symptoms. GDM was defined as altered glucose metabolism requiring dietary or insulin treatment. GDM was detected by a 2 h oral glucose tolerance test according to the recommendations of the Finnish Diabetes Association as well as international recommendations (Metzger and Couston 1998Go). Intrahepatic cholestasis of pregnancy (ICP) was defined as elevated hepatic transaminases and/or elevated serum bile acids.

Municipal maternal healthcare centres (MHC) are the primary care units for pregnant women and are run by public health nurses supervised by general practitioners. This service is free of charge, available to all pregnant women and subsequently utilized by >99% of pregnant women. At each visit to the MHC, the measures and course of the pregnancy are documented in a standardized, nationally used medical record. Women carry a copy of the record, and care given outside the MHC is marked on it. The content of the maternity record is copied to hospital records. If a problem is detected in the course of pregnancy, the patient is referred to an obstetric out-patient clinic located in a hospital. There is one university central hospital, three central hospitals and two regional hospitals in Northern Finland. No private hospitals are located in this area.

For statistical methods, RRs with 95% confidence intervals (CIs) were used for categorical variables and proportions of fourths (quartiles as cut-offs) for continuous variables with Mann–Whitney U-tests. The main analyses were stratified by plurality. Whenever all mothers were presented together (Table IGo), the analyses were adjusted for the number of fetuses. Success in matching was explored and it developed that we were unable to fully follow the matching criteria of the area of residence because there were not enough eligible spontaneous multiple pregnancies for the control group in the area in question. We faced the problem of small numbers of triplet and quadruple pregnancies and consequently they were excluded from further statistical analyses. However, triplet pregnancies were included in the maternal background analysis. We were unable to trace pregnancy data on two IVF women. However, other appropriate data were available for them. The data on specific variables were missing on average in 2% of the women, and consequently the numbers vary slightly, variable by variable. Maximum numbers are given in the tables.


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Table I. Maternal characteristics of IVF and control mothers in Northern Finland in 1990–1995 by fetal plurality. Values are n (%)
 

    Results
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
Background characteristics
In the IVF group, 225 women (223 with all data, two without pregnancy data) gave birth to 305 liveborn and three stillborn (one twin and two triplets) children. The IVF group consisted of 153 singleton pregnancies, 62 twin pregnancies, nine triplet pregnancies and one quadruplet pregnancy. We were able to obtain information on 671 control pregnancies, including 580 singleton pregnancies, 82 twin pregnancies and nine triplet pregnancies.

Maternal characteristics are presented in Table IGo by fetal plurality. As a result of matching, the mean ages of the two groups were the same (IVF mothers 31.8 years, range 23–40; control mothers 31.8 years, range 19–40). The majority of women were primiparous. There was one previous IVF delivery in both groups. The most common pre-existing disease was arterial hypertension in both the IVF and control groups. After adjusting for fetal plurality, the history of pregnancies showed differences between the groups; slightly more (not significant) spontaneous abortions, 20 versus 18% (RR 1.3, 95% CI 0.9–1.7), and significantly more ectopic pregnancies, 21 versus 2% (RR 11.3, 95% CI 6.2–20.4), were seen in the IVF group. Unadjusted figures were substantially similar. The aetiology of infertility varied: tubal occlusion 41%, unexplained infertility 25%, male factor infertility 16% and others (endometriosis, mixed aetiology, hormonal) 17%.

Pregnancy complications
Early pregnancy bleeding, as well as second and third trimester bleeding, was significantly more common both in the IVF singleton and twin groups than in the control groups. When the cases of vanishing embryos in the IVF group (six in singletons and three in twins) were excluded from the analysis, the differences remained significant (RR 3.2, 95% CI 1.9–5.5 for singletons; RR 6.0, 95% CI 2.1–16.7 for twins). No difference in the incidence of chorionamnionitis was found between the groups. The incidence of threatened preterm birth, i.e. preterm uterine contractions with or without preterm cervical ripening needing specialized care, was significantly more common among IVF singleton pregnancies than among controls. The risk of preterm premature rupture of the (fetal) membranes (PPROM) was analysed separately, being non-significantly higher in the IVF singleton group than in the control group (RR 3.8, 95% CI 0.8–18.6). The twin pregnancies showed no difference in this respect. The occurrence of PIH was similar in both singleton and twin comparisons.

An increase in the incidence of GDM was seen both in IVF singleton and twin groups compared with controls, even though this was not statistically significant, possibly partly due to imprecise estimates shown in rather wide CIs. The incidence of ICP was nearly 4-fold higher (although only marginally statistically significant) in singleton IVF pregnancies (RR 3.8, 95% CI 1.0–15.0). For twin pregnancies there was a trend towards an increased incidence of ICP in the IVF group, but the difference did not reach statistical significance. The incidence of IUGR was non-significantly lower in the singleton IVF group than in the control group (Table IIGo). There were three cases with placental complications, i.e. three placenta praevias (one in the singleton group, two in the twin group), but no abruptions occurred in the IVF group. One abruption occurred in the whole control group. The incidence of pregnancy complications was also compared between different infertility groups. Infertile patients with hormonal infertility seemed to be more predisposed to GDM than patients with tubal infertility (RR 5.8, 95% CI 1.3–27.0). No other significant differences were found (data not shown).


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Table II. Pregnancy complications in singleton and twin IVF and control pregnancies in Northern Finland in 1990–1995. Values are n (%) unless otherwise specified
 
Antibiotics were more commonly used in the singleton IVF group than in controls (Table IIGo). The most common indications for antibiotic treatment during pregnancy were respiratory and urinary tract infections in both IVF and control groups.

The mean ± SD gestational ages at birth did not differ between the IVF and control groups either among singleton (38.9 ± 2.6 versus 39.3 ± 1.9 weeks) or twin pregnancies (36.2 ± 2.1 versus 36.0 ± 2.8 weeks). The risk of preterm birth before the beginning of week 32 of gestation was slightly, but not significantly, elevated for IVF singletons (RR 1.9, 95% CI 0.5–7.4). In control twins, the risk for preterm birth before week 32 of gestation was higher than in IVF twins, but due to small numbers the estimate was imprecise (RR 0.2, 95% CI 0.02–1.5). Gestational lengths at delivery were also analysed at 32–36, 37–42 and >42 weeks, but no statistically significant differences were found in any comparisons (data not shown).

Delivery
There were no differences in the mode of delivery between the IVF and control groups. For singletons, the Caesarean section rate was 25% in both IVF and control groups. For firstborn twins the rate was 53% (IVF) versus 46% (controls).

Neonatal outcome
Specific neonatal data have been previously presented (Koivurova et al., 2002Go). As a whole (all IVF children compared with controls representing the general population in proportion of multiple births), IVF neonates had a significantly worse outcome in terms of low/very low birth weight and neonatal morbidity than control neonates. IVF children were more often hospitalized during the neonatal period than the controls and, in addition, the perinatal and neonatal mortality as well as the stillbirth rates were higher than in the general population. The incidence of heart malformations, but not of other malformations, was significantly higher in the IVF group. The analyses stratified by plurality showed no significant differences.

Use of maternal healthcare services
There were no differences in the number of MHC visits between the IVF and control groups (mean ± SD, 12.6 ± 3.3 versus 13.1 ± 3.4 for singletons; 9.2 ± 2.9 versus 9.1 ± 3.3 for twins), but both singleton and twin IVF mothers had significantly more contact with hospital out-patient clinics during pregnancy than controls (5.7 ± 3.7 versus 2.4 ± 2.6 for singletons; 10.6 ± 3.5 versus 6.8 ± 2.9 for twins). The length of antenatal hospitalization was longer for singleton IVF mothers when compared with controls (3.5 ± 6.7 versus 2.4 ± 5.4 days), but the length of post-partum hospitalization was similar (7.0 ± 2.0 versus 6.8 ± 1.9 days). For twin mothers, there were no significant differences in the length of antenatal hospitalization (14.1 ± 21.9 versus 10.1 ± 14.0 days), but the length of post-partum hospitalization was, in turn, longer for IVF twin mothers than for controls (10.1 ± 2.7 versus 9.1 ± 2.7 days) (Table IIIGo).


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Table III. The use of antenatal health services in singleton (IVF, n = 153; control, n = 580) and twin (IVF, n = 62; control, n = 82) pregnancies in Northern Finland in 1990–1995
 

    Discussion
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
The advantage of the present study is that it is a population-based cohort study including all IVF pregnancies in a certain area and time period leading to delivery, with a matched control group consisting of women derived from the national birth register. Therefore, the control group is not a selected one, e.g. from hospitals or special clinics, but represents the population at large matched for age, parity and social class distribution, eliminating the potential risk of bias. Matching for region was not possible for every mother, but due to the uniform MHC system in the country, we have assumed that it does not cause any major bias. Power calculation indicated a relatively high power to detect differences between the major pregnancy complications. However, it is evident that for the most rare events, even these numbers are low.

With ageing the risk of pregnancy complications increases considerably, advanced age being a common characteristic of infertile women. Maternal age >35 years has also been found to relate to poor neonatal outcome (Sipilä et al., 1994Go). An increased incidence of pregnancy complications has been linked to IVF pregnancies, probably resulting from the maternal characteristics regarding infertility and the excess of multifetal pregnancies following IVF. The matching for age and parity was based on the fact that older women carry additional risks, and the aim was to study IVF pregnancies in spite of advanced age and primiparity. Therefore, the control mothers do not represent typical Finnish mothers, who are on average 27.6 years at first delivery (FMBR, unpublished data), but women having their first child at a late age. Therefore, the comparison does not reveal the extra difficulties of IVF mothers compared with an average population of childbearing age.

The main difference in the obstetric history was that IVF mothers had more previous spontaneous abortions, probably reflecting their poorer ability to maintain pregnancy. On the other hand, the excess of ectopic pregnancies may be a consequence of impaired tubal function as a cause of infertility.

We found an increased incidence of uterine bleeding during all trimesters in IVF pregnancies, even when cases with vanishing embryos were excluded. A previous study reported similar results (Koudstaal et al., 2000bGo). They concluded this phenomenon to be a result of more exact early antenatal surveillance, a higher incidence of placenta praevia and preterm uterine contractions in IVF pregnancies. This is supported by our results, with the exception of placental complications. One might speculate that uterine bleeding may also be a consequence of the IVF procedure itself in form of impaired placentation, which might lead to an increase in the incidence of low-lying placentas, though no direct conclusion can be drawn from this study. An association between IVF and placenta praevia has been found by others (Tan et al., 1992Go; Tanbo et al., 1995Go). The previously noted elevation of serum hCG at mid-trimester in IVF pregnancies may also reflect the poorer placentation following ART (Heinonen et al., 1996Go).

An increased risk of preterm birth has previously been noted to be associated with second trimester bleeding (Sipilä et al., 1992Go) and hypertension during pregnancy (Doyle et al., 1992Go). A significantly higher incidence of threatened, though not actual, preterm birth among singleton IVF pregnancies was seen in our study, confirming previous studies that indicate an increase in the incidence of actual preterm birth (Tan et al., 1992Go; Wang et al., 1994Go; FIVNAT, 1995Go; Tallo et al., 1995Go; Tanbo et al., 1995Go; Koudstaal et al., 2000bGo). The incidence of chorionamnionitis, which is an important factor behind preterm birth, was similar between the IVF and control singleton groups. However, the RR of PPROM was nearly 4-fold among IVF singletons, but did not reach statistical significance.

Some studies have not found any differences in the gestational length at birth between IVF and spontaneous pregnancies (Olivennes et al., 1993Go; Reubinoff et al., 1997Go), which was supported by the present study at this age range of mothers. We also stratified the data by gestational length and no consistent pattern was found. The singleton IVF deliveries before the beginning of week 32 of gestation were slightly more common than in the comparison cohort, but due to small numbers the estimates are fairly imprecise. The minor differences in the gestational length between IVF and control groups may partly be related to the study design itself (matching), indicating that factors other than IVF technology might be more important determinants of preterm birth.

With the exception of bleeding during pregnancy, the course of pregnancy was found to be similar in IVF and control twin pregnancies in our study. These results are in accordance with previous publications (Olivennes et al., 1996Go; Ágústsson et al., 1997Go), although increased risk for preterm birth (Moise et al., 1998Go; Lambalk and van Hooff, 2001Go), lower average birth weight (Koudstaal et al., 2000aGo; Lambalk and van Hooff, 2001Go), pregnancy complications and adverse perinatal outcome (Daniel et al., 2000Go), and discordant birth weight (Bernasko et al., 1997Go) in IVF twin pregnancies have also been found.

No significant difference in the incidence of PIH between IVF and control groups was found, suggesting that PIH as such is not related to IVF technology, but rather to the other risk factors these women represent. These results are in accordance with many previous publications (Verlaenen et al., 1995Go; Reubinoff et al., 1997Go; Koudstaal et al., 2000bGo). However, some investigators have found PIH to be more common in ART pregnancies (Tallo et al., 1995Go; Tanbo et al., 1995Go), suggesting that either ART or infertility might predispose for PIH (Tanbo et al., 1995Go). Both of these studies were matched for maternal age, but only Tanbo’s study was also matched for parity.

The incidence of GDM was non-significantly higher among IVF pregnancies than controls in our study. It is suggested that this phenomenon might be related to a high prevalence of polycystic ovarian syndrome (PCOS) among infertile patients or to an ovulation stimulation agent (Maman et al., 1998Go). PCOS is known to be associated with insulin resistance, as is pregnancy itself. Correspondingly, our results showed a higher risk for GDM in patients with hormonal infertility when compared with patients with tubal infertility (RR 5.8, 95% CI 1.3–27.0). On the other hand, most other studies have found no increase in GDM among IVF-treated women (Tallo et al., 1995Go; Reubinoff et al., 1997Go; Koudstaal et al., 2000).

The estimate of RR of ICP for IVF pregnancies was, in terms of statistical significance, imprecise. However, even in this relatively small population-based sample the risk was multiple compared with controls. Its clinical importance should therefore be noted. Previous studies have not reported this phenomenon, possibly due to the rarity of ICP in most countries, with an incidence ranging from 1 in 1000 to 1 in 10 000 deliveries (Davidson, 1998Go). However, in Sweden and Finland the occurrence is almost 2% of deliveries (Reyes and Simon, 1993Go) for unknown reasons. ICP is a severe clinical problem in our country, with a risk of fetal death at the end of third trimester. The reasons for the association between IVF and ICP are unclear, but they could be related to some metabolic disturbances regarding infertility itself.

Antibiotic treatments were more common in the singleton IVF group than in the control singleton group. It can be speculated that antibiotics are prescribed more easily to IVF mothers with more loose indications, which reflects the ‘value’ of these pregnancies.

We found no differences in the mode of delivery between IVF and control groups, but the Caesarean section rate was very high even in singleton pregnancies (25% in both groups). The section rate for singleton pregnancies in the general population in Northern Finland during the same time period was 13%. However, in primiparous women >30 years of age the section rate in Finland during 1991–1995 was 27%, a similar magnitude to that of our study (FMBR, unpublished data). It is likely that it is not IVF itself that leads to an increased number of Caesarean deliveries, both elective (Tanbo et al., 1995Go; Verlaenen et al., 1995Go; Reubinoff et al., 1997Go) and emergency (Olivennes et al., 1996Go; Reubinoff et al., 1997Go), among IVF pregnancies, but other relating background factors, such as being an old primipara or having a multiple pregnancy. It is probable that pre-existing difficulties of having a child make these pregnancies so-called ‘precious pregnancies’, which may in some societies lead to an increased rate of Caesarean sections both through the decision of the parents and obstetricians.

Neonatal data has been previously discussed in detail (Koivurova et al., 2002Go).

Few studies have been conducted on the use of antenatal care in IVF pregnancies. According to a Finnish study, IVF singleton mothers had more antenatal care visits than others and the intensity of their use of antenatal care was 17% higher (Gissler et al., 1995Go). A high rate of hospitalization during pregnancy has been found in IVF pregnancies (Friedler et al., 1992Go; Gissler et al., 1995Go; Nuojua-Huttunen et al., 1999Go). In the present study, singleton and twin IVF mothers had more antenatal visits to hospital out-patient clinics than controls. However, there were no differences in the number of MHC visits, MHC being the primary place of antenatal care. This suggests that IVF mothers are referred to specialized obstetric care more easily than mothers with spontaneous pregnancies. The length of hospitalization during pregnancy was longer for singleton IVF mothers than for controls. Due to the very uniform MHC system in our country, we can assume that there was no major bias in referring the patients to specialized care from different MHCs. It is probable that the increased use of specialized antenatal care is partly due to the maternal characteristics regarding infertility. In addition, the perception of an IVF pregnancy as a risk pregnancy and parental wishes for careful pregnancy surveillance may increase the use of antenatal services.

In conclusion, we have shown an increased risk for vaginal blood loss throughout pregnancy and threatened preterm birth in IVF pregnancies, as was expected in our hypothesis. In addition, a trend towards an increased risk for ICP among IVF pregnancies was found. The incidence of other pregnancy complications was more prominent in singleton than in twin IVF pregnancies when compared with controls. Therefore, it can be speculated that the effect of multiplicity is stronger than the effect of IVF technology on the course of pregnancy. In addition, this study sheds light on the cost for society after IVF treatments, presenting the more frequent use of specialized maternal healthcare services among IVF mothers when compared with control mothers. This in turn raises the cost of healthcare in general. In order to improve the outcome of IVF pregnancies, the incidence of multiple pregnancies as a consequence of ART should be reduced to a minimum by replacing as few embryos as possible, preferably only one embryo. As IVF singleton pregnancies also seem to be prone to certain obstetric risks, these pregnancies need a close antenatal follow-up.


    Acknowledgements
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
We gratefully acknowledge the important advise of Ulla Sovio, MSc on statistical matters. This study was financially supported by The Alma and K.A.Snellman Foundation, Oulu Finland and by the National Social Insurance Institute, Finland.


    Notes
 
6 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, University Hospital of Oulu, P.O.Box 24, 90029 Oulu, Finland. E-mail: sari.koivurova{at}oulu.fi Back


    References
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
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Submitted on March 21, 2001; resubmitted on March 14, 2002; accepted on July 16, 2002.