Hum. Reprod. Advance Access originally published online on November 25, 2005
Human Reproduction 2006 21(3):713-720; doi:10.1093/humrep/dei390
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Antenatal care in singleton pregnancies after ICSI as compared to spontaneous conception: data from a prospective controlled cohort study in Germany
1 Department of Gynaecology and Obstetrics, 2 Institute of Cancer Epidemiology and Institute of Social Medicine, University of Schleswig-Holstein, Campus Lübeck, 3 Congenital Malformation Monitoring-Centre Saxony-Anhalt, Faculty of Medicine, Otto-von-Guericke University Magdeburg and 4 ENDOKRINOLOGIKUM Hamburg, Zentrum für Hormon- und Stoffwechselerkrankungen, Reproduktionsmedizin und Gynäkologische Endokrinologie, Germany
5 To whom correspondence should be addressed at: Department of Gynaecology and Obstetrics, University of Schleswig-Holstein, Campus Lübeck Germany, Ratzeburger Allee 160, 23538 Lübeck, Germany. E-mail: A.K.Ludwig{at}web.de
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
|---|
BACKGROUND: The aim was to compare the antenatal care and the intake of vitamins and medications of infertility patients with singleton pregnancies after ICSI to women with a spontaneously conceived singleton pregnancy. METHODS: The data on the antenatal care of 2055 singleton pregnancies after ICSI from a prospective controlled multicentre study in Germany were analysed. The prospectively collected data of the control group of 7861 singletons were retrospectively assessed for the present analysis. RESULTS: The ICSI patients were significantly older (32.9 versus 27.0 years, P < 0.019) and more likely to be obese (body mass index
30 kg/m2: 13.9 versus 4.8%, P < 0.001) than the controls. The control mothers were significantly more likely to smoke (19.2%) or to consume alcohol (23.5%) during pregnancy than the ICSI mothers (7.4 and 0.6% respectively). Only 38.1% of ICSI patients took folic acid before conception. Only 61.7% of ICSI patients received an iodine supplementation at some point during pregnancy. ICSI patients went more regularly to the routine antenatal care consultations at the gynaecologist and had ultrasound examinations performed more regularly than the controls. The absolute number of ultrasound examinations was significantly higher in the ICSI group (13.6 ± 6.0 versus 4.1 ± 2.4). CONCLUSION: In spite of the intensive use of antenatal medical care by patients pregnant after ICSI, simple methods, such as the use of supplementary iodine and periconceptional folic acid, were used rarely. This indicates that counselling pregnant patients after ICSI about periconceptional and antenatal care seems to be insufficient in Germany and must be improved.
Key words: antenatal care/follow-up/ICSI/medication/pregnancy complication
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
|---|
Several studies have been published on the postnatal utilization of health care facilities and hospitalization of children after assisted reproductive technologies. On the one hand these data concentrated on the concerns about the children’s health and on the other hand on the investigation of the socio-economic health care costs caused by assisted reproductive technologies (Gerris et al., 2004
; Koivurova et al., 2004; Lukassen et al., 2004).
An increase in hospitalization in the neonatal and postnatal phase is caused by the high frequency of multiple pregnancies, the increased risk of prematurity or low birthweight even in singletons and a higher rate of complications during pregnancy (Helmerhorst et al., 2004; Jackson et al., 2004). In addition to this, it has been discussed whether, after a long period of involuntary childlessness, concerned or overprotective parents might use health care resources more extensively or might have a lower threshold level before presenting their child to health care facilities for even minor problems (Ericson et al., 2002).
No sufficient data are available about periconceptional and antenatal care outside invasive (Bonduelle et al., 2002) and non-invasive prenatal diagnostic procedures (Geipel et al., 1999, 2004). It might be assumed that after a long period of living in preparation for a possible pregnancy, patients should ideally be prepared in terms of periconceptional intake of folic acid, having quit smoking before pregnancy or having lost weight. The inability to conceive continues to affect the current life of many lVF patients even after having become pregnant. Many IVF patients are very anxious about the possible loss of their pregnancy and therefore experience their pregnancy as very stressful (Hjelmstedt et al., 2003, 2004). This might lead to a very intensive antenatal care of those patients.
In order to investigate the antenatal care of infertility patients with pregnancies after ICSI in comparison to women with a spontaneously conceived pregnancy, data about the pregnancies were obtained prospectively in a prospective controlled multicentre study in Germany. Multiple pregnancies were excluded from this analysis because of the well-known necessity of a more intense antenatal care in these pregnancies. Those data from such a large cohort of prospectively included and studied patients are not yet available from the literature. For Germany, there are currently no data on this question.
|
Materials and methods |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
|---|
Data of the ICSI cohort were collected prospectively. The prospectively collected data of the control group were retrospectively assessed for the present analysis. The study protocol has been described before (Ludwig and Katalinic, 2002
; Katalinic et al., 2004) and was approved by the ethical committee of the Medical University of Lübeck, Germany.
Briefly, 3198 patients who had conceived after ICSI were recruited for participation before the 16th week of gestation and gave their written informed consent. Recruitment was performed from August 1998 to August 2000. All recruited couples were contacted by telephone in the 16th week of gestation to clarify whether the pregnancy was still ongoing. In cases of an ongoing pregnancy the patients were included in the study and the first data assessment was performed. The patients with a singleton pregnancy were contacted for the second time in the 28th week of gestation. From that point on, the patient was contacted every 2–4 weeks until delivery. After the delivery a final contact was performed by telephone. At this contact an appointment was arranged with one of 25 doctors who were involved in the standardized examination of the newborn. This examination was performed 6–8 weeks postpartum. The examination procedure and data assessment during examination as well as the results of the children’s examinations have been published recently (Katalinic et al., 2004). The control group of spontaneously conceived pregnancies and newborn infants had been included and examined prospectively between January 1993 to December 2001. This cohort was examined according to the same protocol as the study group as described before (Katalinic et al., 2004). The mother’s history including chronic diseases, medications, abuse of alcohol, drugs or nicotine and outcome of former pregnancies as well as prenatal examinations including regular antenatal controls, regular ultrasound, the total number of ultrasound examinations in pregnancy and amnioncentesis were obtained and registered for each control child. The control group included a total of 7941 live births born in the area of Magdeburg in the time period from January 1993 to December 2001. Children born after any infertility treatment were excluded.
The indication for performing ICSI was mainly a severe oligoasthenoteratozoospermia (77.8%). The other indications included obstructive azoospermia (2.7%), non-obstructive azoospermia (3.3%), no fertilization following IVF (8.0%) and other indications (8.0%). However, a decision to perform ICSI was made by each centre based on their own criteria.
The risk profiles of ICSI and control mothers resulting from the mothers’ medical and obstetric history as well as factors resulting from events during pregnancy were compared. The risk profile was analysed by using the checklist of risk factors that is assessed for every pregnancy in the mother’s personal maternity log according to the German motherhood guidelines.
The data about the antenatal care of singleton pregnancies were analysed and compared to the antenatal care of the spontaneously conceived singleton pregnancies in the control cohort. All multiple pregnancies were excluded from both cohorts for the present analysis to avoid the bias of this important influencing factor.
Regarding the intake of medications during pregnancy, only data for the ICSI group are available. Therefore these data are compared with the literature.
Statistics
Differences between the groups were analysed with Kruskal–Wallis test and Mann–Whitney U-test for unpaired samples. For qualitative variables we used contingency tables with 
2-test. Statistical significance was assumed at P < 0.05. Data were recorded within a Microsoft Access database and evaluated with the personal computer-based program SPSS 13.0 (SPSS, Chicago, IL, USA).
|
Results |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
|---|
In all, 2055 women who conceived a singleton pregnancy after ICSI and 7861 control patients with a singleton pregnancy who had conceived spontaneously were included in the analysis. Regarding the patients’ histories, according to the risk profile that is assessed in the maternity log, there were slight differences between the two groups (Table I). The ICSI patients were significantly older as compared to the controls (32.9 ± 3.9 versus 27.0 ± 4.7 years, P < 0.01) and significantly more likely to be obese (body mass index (BMI)
30 kg/m2: 13.9% versus 4.8%, P < 0.001). More ICSI mothers had a history of uterine surgery (other than Caesarean section) and more ICSI mothers were rated to suffer from a high psychological burden, while more control mothers were rated to suffer from a high burden caused by their personal social or socio-economic circumstances. The rating of a high psychological or social burden was performed by the patient’s gynaecologist on his knowledge in the maternity log. Significantly more control mothers had diabetes mellitus (type 1 or 2) compared to the ICSI group (0.6 versus 0.3%, P = 0.001).
|
Regarding the patients’ risk profile resulting from previous pregnancies, more control mothers presented with risk factors. More control mothers had a short interval between the previous and the present pregnancy (<1 year), a history of a stillbirth or a birth of a sick child or a history of 2 abortions. Complications during a previous pregnancy had occurred more often in those actually pregnant after ICSI. These data were published previously (Katalinic et al., 2004).
The controls were significantly more likely to smoke or to consume alcohol during pregnancy than the ICSI patients. Most ICSI patients who smoked during pregnancy smoked a maximum of 10 cigarettes daily (53.9% 1–5 cigarettes/day, 28.3% 6–10 cigarettes/day), only 12.5% of those who smoked consumed 10–20 cigarettes and 5.3% smoked >20 cigarettes/day. Twelve women (0.6%) of the ICSI group reported having drunk alcohol during pregnancy compared to 23.5% in the control group (Table II). The sub-analysis of smoking on the number of cigarettes per day was not available for the controls.
|
Although the utilization of antenatal care was high for both groups (Table III), the rate of women who went regularly to the routine antenatal consultations at the gynaecologist and the rate of women having regular ultrasound examinations performed were significantly higher in the ICSI group compared to the control group (100 and 99.6% versus 94.4 and 95.0%, P = 0.005 and P = 0.036 respectively). Regular antenatal care consultations were defined as consultations every 4 weeks throughout the pregnancy. Regular ultrasound examinations were defined as one ultrasound being performed in each trimester as suggested by the official guidelines for maternity care in Germany.
|
The absolute number of ultrasound examinations was significantly higher in the ICSI group with a mean number of 13.6 (± 6.0) ultrasounds compared to the control group with a mean number of 4.1 (± 2.4). In 7.4% of the ICSI patients the ultrasound examination revealed a pathological finding such as a signs of major malformations, whereas in the control group only 1.1% of patients had a pathological ultrasound finding (P < 0.005). A total of 27.8% of patients underwent some kind of invasive prenatal diagnosis. The detailed data about the use of invasive prenatal diagnosis have been published recently (Katalinic et al., 2004).
In the ICSI group, 34.1% (687/2023) of patients were hospitalized at some point during pregnancy. The mean duration of hospitalization was 15.3 (± 19.7) days ranging from 1 to 166 days (median: 8 days). In the ICSI group, 28.2% (579/2055) of patients reported some kind of illness not related to pregnancy that required treatment. No data on this question were available for the controls.
In the ICSI group, 16.5% (332/2014) of patients required medical tocolytic therapy; of these, 9.2% (186/2014) received an oral tocolytic therapy for the mean duration of 44.7 (± 37.5) days. The duration of the oral tocolytic therapy ranged from 1–196 days. Twelve patients took tocolytic medications only in the second trimester, 142 only in the third trimester and 32 patients in the second and third trimester. A total of 146/2014 (7.3%) patients received an intravenous tocolytic therapy for the mean duration of 17.6 (± 21.7) days, varying from 1 to 122 days; of these, 23 patients received intravenous tocolytic therapy only in the second trimester, 110 in the third and 12 in the second and third trimesters.
Information about periconceptional medication with folic acid was available for 1994 ICSI patients (97.0%); of these, 38.1% (760/1994) took folic acid already before conception. This information was not available for the control group. All data for medication intake during pregnancy for the study cohort are shown in Table IV and Figure 1.
|
|
The pregnancy outcome of both groups is shown in Table V. More detailed data on the outcome and on the malformation rates have been previously published (Katalinic et al., 2004).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
|---|
The present analysis on the antenatal care of 2055 singleton pregnancies after ICSI and 7861 spontaneously conceived singleton pregnancies revealed significant differences in the risk profile assessed in the maternity log. Antenatal care by ultrasound and visits with the obstetrician was more intense in the ICSI cohort. ICSI patients overall took significantly more medication during pregnancy. However, simple methods such as periconceptional folic acid supplementation and iodide supplementation during pregnancy were far from optimal even in these planned high risk pregnancies.
More ICSI pregnancies were considered to have risk factors based on the mother’s medical condition, while the control pregnancies had more risk factors resulting from the mother’s obstetric history. In the ICSI group, the rate of patients with a history of uterine surgery was higher than in the control groups which might be caused by a higher rate of uterine fibroma and endometriosis. However, we cannot provide data to explain this difference. The ICSI patients were more often obese than the control women. As obesity is known to decrease the fertility potential of a woman, the woman’s obesity might—in addition to a male factor—have contributed to the couple’s infertility.
Deliberately, the risk factors resulting from previous pregnancies were not calculated based only on those women with previous pregnancies, but were based on all women in each group. The aim of this calculation was not to estimate the number of complications during a previous pregnancy, but to analyse the number of pregnancies that had to be rated as pregnancies at risk because of complications during previous pregnancies. It has to be noted that the incidence of socio-economic problems, diabetes and teenage pregnancies was significantly higher in the control group, as all of these factors are associated with an increased risk of developing pregnancy complications.
Significantly fewer women in the ICSI group consumed cigarettes or alcohol during pregnancy compared to the control group. None of the ICSI mothers consumed any kind of illegal drugs. The rate of 7.4% of ICSI mothers smoking during pregnancy is in accordance with some studies on smoking in pregnancies after assisted reproduction. However, the numbers found in the literature vary. In the studies available, 5–17% of IVF or ICSI patients are reported to smoke during pregnancy and 10% to drink alcohol during pregnancy compared to 8–18% (Sutcliffe et al., 2001; Bonduelle et al., 2004, 2005; Koivurova et al., 2004) and 11% of the control group respectively (Bonduelle et al., 2004, 2005). Only Sutcliffe et al. (2001) found that as many as 68.8% of ICSI patients and 63.8% of control women drank alcohol during pregnancy (difference not significant). Interestingly, most studies did not show a difference in smoking or alcohol consumption between mothers who conceived after assisted reproduction and mothers who conceived spontaneously (Nuojua-Huttunenet al., 1999; Koivurova et al., 2002; Bonduelle et al., 2004, 2005). Overall, patients pregnant after ICSI seem to be well informed about the problems of smoking, alcohol and illegal drug abuse during pregnancy.
Significantly more ICSI than control mothers regularly went to antenatal care visits to their physician (100 versus 94.4%) and had ultrasound examinations performed regularly (99.6 versus 95.0%). The mean number of ultrasound examinations preformed was much higher in the ICSI group (13.6 versus 4.1). This big difference cannot be explained only by the significantly higher number of pathological findings on ultrasound in the ICSI group (7.4 versus 1.1%) requiring more control examinations. The high number of ultrasound examinations might reflect the patients’ anxiety and the doctors’ attempts to observe these pregnancies especially carefully. Probably, in most ICSI pregnancies there was an ultrasound examination performed at each antenatal care visit. Furthermore, the suspected higher risk of major malformations might have influenced the physician’s decision to do ultrasound examinations more regularly. The now proven higher risk of major malformations in ICSI (Rimm et al., 2004; Hansen et al., 2005) as well as in conventional IVF pregnancies (Lie et al., 2004) explains the higher rate of pathological findings during ultrasound examinations. The higher rate of intrauterine growth retardation and pre-eclampsia also contributes to the higher rate of abnormal ultrasound findings (Helmerhorst et al., 2004; Jackson et al., 2004).
Unfortunately we cannot provide the absolute number of antenatal care visits at the obstetrician for any of the two groups. However, the difference regarding pregnancy complications may contribute to the big difference in the number of ultrasound examinations. The higher rate of complications during pregnancy may have resulted in one-third of all ICSI mothers being hospitalized during pregnancy. In the retrospective analysis mentioned above, Koivurova et al. (2002) reported no difference in the mean number of health care service visits between IVF and control mothers (12.6 versus 13.1), but more visits in hospital outpatient clinics during IVF pregnancies compared to control pregnancies (5.7 versus 2.4, P < 0.0001). They also found a longer mean duration of antenatal hospitalization in IVF mothers than in control mothers (10.4 versus 2.4 days, P < 0.001). However, pregnancy complications which might result in more and longer hospitalizations were also observed more often in the IVF pregnancies. The risk of preterm labour [14.7 versus 8.4%, relative risk (RR): 1.8; 95% confidence interval (CI): 1.1–2.9] and 1st trimester bleeding (10.7% versus 1.6%, RR: 6.7; 95% CI: 3.0–15.0) and 2nd and 3rd trimester bleeding (8.7 versus 3.2%, RR: 2.7; 95% CI: 1.4–5.5) were higher in the IVF group than in the control group (Koivurova et al., 2002).
The same group (Koivurova et al., 2004) calculated the health care costs for 152 IVF singletons and 62 IVF twins and 285 spontaneously conceived singletons and 82 twin pregnancies. The health care costs until the end of the neonatal period were 1.3-fold for IVF singletons and 1.1-fold for IVF twins compared to control singletons and twins.
Klemetti et al. (2002) conducted a retrospective analysis based on the Finnish medical birth registry and found that from 1998 to 1999, 39.5% of IVF and ICSI singleton mothers were hospitalized during pregnancy compared to 20.8% of singleton mothers who had conceived spontaneously. The mean number of antenatal care visits in this study was non-significantly higher for the IVF and ICSI pregnancies compared to the control pregnancies (19.4 versus 16.5). Another cohort study (Nuojua-Huttunen et al., 1999) based on the Finnish medical birth registry compared the number of antenatal care visits during pregnancies after intrauterine inseminations (IUI), IVF and spontaneous conception and found that the number of antenatal care visits during IVF singleton pregnancies was significantly higher than during IUI or spontaneously conceived singleton pregnancies (18.1 versus 16.2 and 15.8, P < 0.01). The percentage of women hospitalized during pregnancy was not different between IVF, IUI and spontaneously conceived pregnancies (28.3, 27.9 and 34.1%).
We found 34.1% of patients in the ICSI group to be hospitalized at least once during pregnancy, which is in the range of data published by Nuojua-Huttunen et al. (1999) and Klemetti et al. (2002). Data on the mean duration of hospitalization in singleton pregnancies, which was 
15 days in our study, are rare in the world literature. Klemetti et al. reported a mean duration of 6.1 days for IVF singleton pregnancies and 4.5 for spontaneously conceived singleton pregnancies. Koivurova et al. (2002) found a median of 1.0 day for IVF and spontaneously conceived singleton pregnancies; however, the 75th quartiles differed between the groups with 4.0 and 2.0 days respectively.
Of the ICSI pregnancies, 27.8% underwent invasive prenatal diagnosis, revealing a pathological finding in 2.5% of these examinations. Although we cannot provide this information on the control group, one has to keep in mind that 33.9% of ICSI mothers are aged >35 years compared to only 4.8% of control mothers. The percentage of patients who chose prenatal diagnosis was comparable to that reported in other studies (Loft et al., 1999; Westergaard et al., 1999; Koudstaal et al., 2000).
As Germany is a country with an iodine deficiency, iodine supplementation is absolutely recommended for all pregnant women. Folate administration substantially reduces the risk of neural tube defects. To prevent these defects, the Public Health Service of the United States (1992) and the Institute of Medicine (1998) issued separate recommendations that all women capable of becoming pregnant consume 400 µg of folic acid daily (Carter et al., 2004). The Food and Drug Administration mandated fortification of cereal grain products with folic acid to increase the women’s daily intake. Fortification of food with folic acid has been widely discussed. However, in spite of fortification of food in the USA not all women receive adequate levels of folic acid with their diet. Especially low-carbohydrate diets can reduce the intake of fortified and folate-rich food (Carter et al., 2004). In Germany, fortification of food is not performed. Therefore, the intake of 400 µg of folic acid is recommended preconceptionally (6 weeks before conception) and during the pregnancy.
Little is known about the intake of vitamins and medications during pregnancy after assisted reproduction. Two-thirds of all ICSI mothers received magnesium during pregnancy. This high rate reflects the anxiety and carefulness of these patients as well as their doctors. Therefore it is surprising that only 75 and 61.7% respectively took supplementary folic acid and iodine at some point during pregnancy, which is recommended for all pregnant women during the whole pregnancy in Germany. It is even more surprising that only 38% of the ICSI patients took folic acid periconceptionally.
There are some studies on intake of folic acid before and during the pregnancy in the general population. In a German study, only 6.0% of women had taken folic acid preconceptionally, and as few as 7.45% of women who had planned their pregnancy had started to take folic acid (Rösch et al., 1999). However, there are no data about the use of folic acid before and during the (planned) pregnancies of infertility patients. The Morbidity and Mortality Monthly Report of the Centre of Disease Control and Prevention reported that 40% of women of childbearing age (20–45 years) in the USA take vitamin supplements containing folic acid. However, only 24% of the women knew that folic acid should be taken for the prevention of birth defects and only 12% knew that it should be taken before pregnancy (Carter et al., 2004).
In the studies published so far, the percentage of periconceptional supplementation with folic acid in the general population ranged between 6 and 25%, and the supplementation during the pregnancy varied between 50 and 60% in the general population (Brandenburg et al., 1999; McDonnell et al., 1999; Braekke and Staff, 2003; Coll et al., 2004; Jaber et al., 2004). A study from Norway found a substantial difference in the consumption of folic acid preconceptionally (22% of non-immigrants and 2% of immigrants) and at some point during the pregnancy (73% of non-immigrants and 19% of immigrants) between immigrants and non-immigrants, indicating the need for education that reaches the whole population (Braekke and Staff, 2003). Compared to the general population, the rate of folic acid periconceptionally and during the pregnancy—38 and 75% respectively—might be assumed to be high. However, these patients accept a stressful therapy and invest a lot of effort in order to conceive. Therefore, it is astonishing that not even half of these patients prepare themselves for a pregnancy by taking folic acid and that one-quarter of these patients do not take supplementary folic acid and iodide once they become pregnant—or may not even be advised to do it by their IVF specialist or general gynaecologist.
Sillender and Pring (2000) analysed the effectiveness of a campaign of the Health Education Authority on the prophylactic use of folic acid by questioning 262 women in the 20th week of gestation. After the campaign, significantly more women had read written material recommending the use of preconceptional folic acid (61.1% rising to 76%, P = 0.02). As a result of this information, the use of preconceptional folic acid increased from 27.1 to 48.0% (P < 0.001). General practitioners were significantly more likely to prescribe folic acid preconceptionally following the campaign (an increase from 3.1% to 14.7%, P < 0.0001). The most common reason for not taking folic acid was unplanned pregnancy (25.5%), non-awareness of folic acid (15.4%), awareness without being convinced of the efficacy (8.3%). Cost was a less important factor (2.1%). This observation demonstrates the effectiveness and the importance of educational campaigns (Sillender and Pring, 2000). However, the benefit of folic acid should also be addressed in personal consultations by the general practitioner or gynaecologist. Especially, infertility patients are consulted several times by their gynaecologist before being referred to an infertility unit. Therefore these opportunities for information and recommendation should be used.
Data on the use of folic acid in pregnancies after assisted reproductive technologies are very rare worldwide. Fawzy and Harrison (1998) checked 281 women for the presence of specific pre-conceptional data prior to commencing an IVF programme. Only 15% of women took folic acid. After including specific advice on the prophylactic use of folic acid in the IVF patients information booklet and after including the advise verbally at the group meeting, the rate of patients taking preconceptional folic acid rose to 65% (after 1–3 months) and to 98% (after 4–6 months) (Fawzy and Harrison, 1998). These data clearly demonstrate that motivated couples will respond positively to information. It has to be kept in mind that couples referred to an infertility unit have gone through a rather long time of trying to conceive and usually several visits to the general gynaecologist or general practitioner who should have informed the patients about the recommendations on the prophylactic use of folic acid and iodine.
In our study, only 1.5% of ICSI mothers did not take any medications during pregnancy. After exclusion of iron, vitamins, iodine and folic acid, 15.5% of women took no medication during pregnancy, 66.9% received 1–3 drugs and 15.2% 4–6 drugs. However, in spite of the official recommendations for iodine substitution, only 31% of pregnant women received iodine, but 76.3% of women received magnesium. There are no data on the intake of medications during pregnancies after infertility treatment. Our results are in accordance with the findings of studies on the general population. In spite of the high effort that is invested in those pregnancies, the counselling of infertility patients during pregnancy seems not to differ from the general pregnant population. However, to date there have been no studies comparing the intake of medications during pregnancies after infertility treatment and spontaneous conception. In a study that analysed prescription data from 41 293 pregnant women, 96.4% were found to have received at least one drug during pregnancy. A median of seven drugs per women was prescribed. Excluding vitamins, minerals, iodine and iron, 85.2% received at least one drug. Magnesium was by far the most frequently prescribed substance, 61% of women received magnesium during pregnancy. 54% iron supplementation. 23% of women received antibiotics during the third trimester (Egen-Lappe and Hasford, 2004). A Brazilian study reported 94.6% of women to have taken at least one medication during pregnancy, but only 27.7% of patients were aware of the risk of taking medication during pregnancy (Fonseca et al., 2002). An American analysis of the databases of 8 health maintenance organizations found that in 64% of 98 182 deliveries a drug other than vitamin or mineral supplement was prescribed. Almost one half of all pregnant women received prescription drugs from categories C, D (fetal risk but benefits may be acceptable), or X (fetal risk outweighs benefits) of the US Food and Drug Administration risk classification system (2.4% received a drug from category A, 50.0% from category B, 37.8% from category C, 4.8% from category D and 4.6% from category X) (Andrade et al., 2004).
The question arises as to why women who have conceived having invested such great time and effort in ICSI treatment are often not counselled appropriately despite the frequent opportunities for counselling. After having presented to their general gynaecologist with infertility, these patients are usually sent to special centres for infertility treatment. They often do not see their gynaecologist again before coming back for antenatal pregnancy care. The division of medical care into the general care before and after infertility treatment and a highly specialized infertility unit may contribute to the suboptimal care. One clinical team expects the other to deal with these evident, but necessary, issues such as a proper counselling.
In summary, more ICSI mothers use the possibilities of antenatal care with regular visits to the obstetrician and with regular ultrasound examinations as compared to those who conceive spontaneously. Due to the higher rate of complications in pregnancies conceived after assisted reproduction treatment, this observation can be easily explained. However, the desire for regular care might also play an important role. The higher rate of complications also might explain why about one-third of patients are hospitalized during pregnancy; however, we do not have sufficient data from spontaneously conceived singleton pregnancies to estimate this.
Patients pregnant after an ICSI procedure take medications in a high number of cases. However, prophylactic care, which could be easily done in these pregnancies, since all of these are planned pregnancies, is far from optimal in Germany. Only 38% of patients who plan to conceive with ICSI use periconceptional folic acid, and once pregnant, only 75% of women use this easy and cheap evidence-based way of primary prevention of neural tube defects. Furthermore, only two-thirds of patients use iodine prophylaxis for their thyroid. Considering the great effort that is needed to achieve these pregnancies, the suboptimal prenatal care is surprising. More intensive counselling of patients is needed in order to optimize the antenatal care in infertility patients.
|
Acknowledgements |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
|---|
We thank all the IVF centres in Germany that recruited the patients for this study. A detailed list of the contributing centres can be found in Ludwig and Katalinic (2002
, 2003) and Katalinic et al. (2004). |
References |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
|---|
Andrade SE, Gurwitz JH, Davis RL, Chan KA, Finkelstein JA, Fortman K, McPhillips H, Raebel MA, Roblin D, Smith DH, Yood MU, Morse AN and Platt R (2004) Prescription drug use in pregnancy. Am J Obstet Gynecol 191,398–407.[Medline]
Bonduelle M, Van Assche E, Joris H, Keymolen K, Devroey P, Van Steirteghem A and Liebaers I (2002) Prenatal testing in ICSI pregnancies: incidence of chromosomal anomalies in 1586 karyotypes and relation to sperm parameters. Hum Reprod 17,2600–2614.
Bonduelle M, Bergh C, Niklasson A, Palermo GD and Wennerholm UB (2004) Medical follow-up study of 5-year-old ICSI children. Reprod Biomed Online 9,91–101.[Web of Science][Medline]
Bonduelle M, Wennerholm UB, Loft A, Tarlatzis BC, Peters C, Henriet S, Mau C, Victorin-Cederquist A, Van Steirteghem A, Balaska A et al (2005) A multi-centre cohort study of the physical health of 5-year-old children conceived after intracytoplasmic sperm injection, in vitro fertilization and natural conception. Hum Reprod 20,413–419.
Braekke K and Staff AC (2003) Periconceptional use of folic acid supplements in Oslo. Acta Obstet Gynecol Scand 82,620–627.[Medline]
Brandenburg H, Traas MA, Laudy J, Ursem N, Westerveld AM and Wladimiroff JW (1999) Periconceptional use of folic acid amongst women of advanced maternal age. Prenat Diagn 19,132–135.[Medline]
Carter H, Lindsey LLM, Petrini JR and Prue C (2004) Use of vitamines containing folic acid among women of childbearing age—United States 2004. Morb Mortality Wkly Rep 53,847–850.
Coll O, Pisa S, Palacio M, Quinto L and Cararach V (2004) Awareness of the use of folic acid to prevent neural tube defects in a Mediterranean area. Eur J Obstet Gynecol Reprod Biol 115,173–177.[Medline]
Egen-Lappe V and Hasford J (2004) Drug prescription in pregnancy: analysis of a large statutory sickness fund population. Eur J Clin Pharmacol 60,659–666.[Medline]
Ericson A, Nygren KG, Olausson PO and Kallen B (2002) Hospital care utilization of infants born after IVF. Hum Reprod 17,929–932.
Fawzy M and Harrison RF (1998) Essential pre-conceptual measures for the female partner before commencing an in vitro fertilisation programme. Ir J Med Sci 167,14–16.[Medline]
Fonseca MR, Fonseca E and Bergsten-Mendes G (2002) [Prevalence of drug use during pregnancy: a pharmacoepidemiological approach]. Rev Saude Publica 36,205–212.[Medline]
Geipel A, Gembruch U, Ludwig M, Germer U, Schwinger E, Dormeier A and Diedrich K (1999) Genetic sonography as the preferred option of prenatal diagnosis in patients with pregnancies following intracytoplasmic sperm injection. Hum Reprod 14,2629–2634.
Geipel A, Berg C, Katalinic A, Ludwig M, Germer U, Diedrich K and Gembruch U (2004) Different preferences for prenatal diagnosis in pregnancies following assisted reproduction versus spontaneous conception. Reprod Biomed Online 8,119–124.[Web of Science][Medline]
Gerris J, De Sutter P, De Neubourg D, Van Royen E, Vander EJ, Mangelschots K, Vercruyssen M, Kok P, Elseviers M, Annemans et al (2004) A real-life prospective health economic study of elective single embryo transfer versus two-embryo transfer in first IVF/ICSI cycles. Hum Reprod 19,917–923.
Hansen M, Bower C, Milne E, de Klerk N and Kurinczuk J (2005) Assisted reproductive technologies and the risk of birth defects—a systematic review. Hum Reprod 20,328–338.
Helmerhorst FM, Perquin DA, Donker D and Keirse MJ (2004) Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies. Br Med J 328,261.
Hjelmstedt A, Widstrom AM, Wramsby H, Matthiesen AS and Collins A (2003) Personality factors and emotional responses to pergnancy among IVF couples in early pregnancy: a comparative study. Acta Obstet Gynecol Scand 82,152–161.[CrossRef][Web of Science][Medline]
Hjelmstedt A, Widstrom AM, Wramsby H and Collins A (2004) Emotional adaptation following successful in vitro fertilization. Fertil Steril 81,1254–1264.[CrossRef][Web of Science][Medline]
Institute of Medicine (1998) Dietary reference intake: Folate, other B vitamins and choline. Washington DC, National Academy Press.
Jaber L, Karim IA, Jawdat AM, Fausi M and Merlob P (2004) Awareness of folic acid for prevention of neural tube defects in a community with high prevalence of consanguineous marriages. Ann Genet 47,69–75.[Medline]
Jackson RA, Gibson KA, Wu YW and Croughan MS (2004) Perinatal outcomes in singletons following in vitro fertilization: a meta-analysis. Obstet Gynecol 103,551–563.
Katalinic A, Rosch C and Ludwig M (2004) Pregnancy course and outcome after intracytoplasmic sperm injection: a controlled, prospective cohort study. Fertil Steril 81,1604–1616.[CrossRef][Web of Science][Medline]
Klemetti R, Gissler M and Hemminki E (2002) Comparison of perinatal health of children born from IVF in Finland in the early and late 1990s. Hum Reprod 17,2192–2198.
Koivurova S, Hartikainen AL, Karinen L, Gissler M, Hemminki E, Martikainen H, Tuomivaara L and Jarvelin MR (2002) The course of pregnancy and delivery and the use of maternal healthcare services after standard IVF in Northern Finland 1990–1995. Hum Reprod 17,2897–2903.
Koivurova S, Hartikainen AL, Gissler M, Hemminki E, Klemetti R and Jarvelin MR (2004) Health care costs resulting from IVF: prenatal and neonatal periods. Hum Reprod 19,2798–2805.
Koudstaal J, Braat DD, Bruinse HW, Naaktgeboren N, Vermeiden JP and Visser GH (2000) Obstetric outcome of singleton pregnancies after IVF: a matched control study in four Dutch university hospitals. Hum Reprod 15,1819–1825.
Lie RT, Lyngstadaas A, Orstavik KH, Bakketeig LS, Jacobsen G and Tanbo T (2004) Birth defects in children conceived by ICSI compared with children conceived by other IVF-methods; a meta-analysis. Int J Epidemiol 34,696–671.
Loft A, Petersen K, Erb K, Mikkelsen AL, Grinsted J, Hald F, Hindkjaer J, Nielsen KM, Lundstrom P et al (1999) A Danish national cohort of 730 infants born after intracytoplasmic sperm injection (ICSI) 1994–1997. Hum Reprod 14,2143–2148.
Ludwig M and Katalinic A (2002) Malformation rate in fetuses and children conceived after ICSI: results of a prospective cohort study. Reprod Biomed Online 5,171–178.[Medline]
Lukassen HG, Schonbeck Y, Adang EM, Braat DD, Zielhuis GA and Kremer JA (2004) Cost analysis of singleton versus twin pregnancies after in vitro fertilization. Fertil Steril 81,1240–1246.[CrossRef][Web of Science][Medline]
McDonnell R, Johnson Z, Doyle A and Sayers G (1999) Determinants of folic acid knowledge and use among antenatal women. J Public Health Med 21,145–149.
Nuojua-Huttunen S, Gissler M and Martikainen H (1999) Obstetric and perinatal outcome of pregnancies after intrauterine insemination. 14,2110–2115.
Public Health Service of the United States (1992) CDC recommendations for the use of folic acid to reduce the number of cases of spine bifida and other neural tube defects. MMWR, 41,no. R–14.
Rimm AA, Katayama AC, Diaz M and Katayama KP (2004) A meta-analysis of controlled studies comparing major malformation rates in IVF and ICSI infants with naturally conceived children. J Assist Reprod Genet 21,437–443.[CrossRef][Web of Science][Medline]
Rösch C, Steinbicker V, Kolbe M, Lehman R and Kötz K (1999) Fehlbildungsprotektion durch Folsäure—Empfehlung und Realität. Gesundheitswesen 61,82–85.[Medline]
Sillender M and Pring MS (2000) How effective was the Health Education Authority’s folic acid campaign? J Obstet Gynaecol 20,271–276.[Medline]
Sutcliffe AG, Taylor B, Saunders K, Thornton S, Lieberman BA and Grudzinskas JG (2001) Outcome in the second year of life after in-vitro fertilisation by intracytoplasmic sperm injection: a UK case–control study. Lancet 357,2080–2084.[CrossRef][Web of Science][Medline]
Westergaard HB, Johansen AM, Erb K and Andersen AN (1999) Danish National In-Vitro Fertilization Registry 1994 and 1995: a controlled study of births, malformations and cytogenetic findings. Hum Reprod 14,1896–1902.
Submitted on July 30, 2005; resubmitted on September 18, 2005; accepted on October 5, 2005.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. McGuire, B. Cleary, L. Sahm, and D.J. Murphy Prevalence and predictors of periconceptional folic acid uptake--prospective cohort study in an Irish urban obstetric population Hum. Reprod., November 12, 2009; (2009) dep398v1. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||