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Obstetric and perinatal outcome of pregnancies after intrauterine insemination

Obstetric and perinatal outcome of pregnancies after intrauterine insemination Abstract The main aim of this study was to evaluate the obstetric and perinatal outcome of pregnancies after intrauterine insemination (IUI) with the partner's spermatozoa combined with ovarian stimulation. Information concerning the antenatal care and obstetric and perinatal outcome of IUI pregnancies (n = 111), spontaneous (n = 333) and in-vitro fertilization (IVF) (n = 333) was obtained from the Finnish Medical Birth Register (MBR). The multiple birth rate in the IUI group was 17% (19/111). Significantly less antenatal care was required by the IUI group than the IVF group. The frequency of Caesarean section was 25% for IUI singletons and 58% for IUI multiples, similar to the other groups. The mean (SD) gestational age for IUI singletons at birth was 39.5 (1.8) weeks, with a mean birth weight of 3285 (575) g, compared with 3448 (600) g in non-assisted singletons (P < 0.05). For IUI multiples the mean gestational age at birth was 36.0 (2.8) weeks and the mean birth weight was 2449 (678) g. The incidence of preterm birth, low birth weight or low Apgar scores and the need for neonatal care were similar in all groups. One case of major malformation and two perinatal deaths were recorded in the IUI group. In conclusion, IUI treatment did not appear to increase obstetric or perinatal risks compared with matched spontaneous or IVF pregnancies. Most problems were associated with patient characteristics and multiple pregnancy. Reduction of the high incidence of multiple pregnancies after assisted reproductive technology is essential to improve its outcome. antenatal care, intrauterine insemination, in-vitro fertilization, obstetric outcome, perinatal outcome Introduction The widespread use of assisted reproductive technology has raised a question about the safety for newborns and mothers. An increased frequency of preterm delivery and low birth weight and a high Caesarean section rate has been found in previous studies on the obstetric outcome of pregnancies after in-vitro fertilization (IVF) compared with natural pregnancies (Doyle et al., 1992; Tan et al., 1992; Gissler et al., 1995; Dawood et al., 1996). The risk of haemorrhage and pregnancy-induced hypertension has been found to be high in pregnancies after assisted reproduction technologies, including oocyte recipients (Tan et al., 1992; Tanbo et al., 1995; Söderström-Anttila et al., 1998). Overall, the high proportion of multiple pregnancies after assisted reproduction technologies increases the rate of obstetric and perinatal complications (Tan et al., 1992; Gissler et al., 1995; Wisanto et al., 1995). However, studies with more strictly matched controls have revealed no differences between pregnancies after assisted reproduction or natural conception (Dhont et al., 1997; Minakami et al., 1998), apart from a higher rate of Caesarean section (Reubinoff et al., 1997; Wennerholm et al., 1997). Intrauterine insemination (IUI) combined with ovarian stimulation remains a widely used treatment option for couples with male factor infertility, ovulatory dysfunction, mild endometriosis or unexplained infertility. Intrauterine insemination is a simpler, less invasive and cheaper first-line treatment than IVF for subfertility, resulting in an acceptable pregnancy rate (PR) of 12–20% per cycle (Dodson and Haney, 1991; Nulsen et al., 1993; Nuojua-Huttunen et al., 1997). The multiple PR varies from 7 to 18% (Nulsen et al., 1993; Brzechffa et al., 1998). Although information concerning the outcome of pregnancies and newborns after infertility treatment is essential, so far, the results of studies of pregnancies after IUI with partner's spermatozoa have not been published. In the present study, we evaluated the obstetric and perinatal outcome of pregnancies after IUI with the partner's spermatozoa. The results were compared with those of matched controls of spontaneous and IVF pregnancies. Materials and methods In total, 125 pregnancies ending in birth (>22 weeks of gestation) were achieved after IUI treatment using the partner's spermatozoa, between March 1991 and December 1996 at the Infertility Clinic of the Family Federation of Finland, Oulu. In all cases, ovarian stimulation was combined with IUI and the most commonly used stimulation protocols were clomiphene citrate (CC) alone (11%) or combined with gonadotrophins (73%). In the remaining cycles, gonadotrophins alone or with gonadotrophin-releasing hormone agonist were used. The indication for IUI treatment was unexplained infertility (where history, physical examination, semen analysis, laboratory assessment of ovulation and tubal patency were normal) in 60%, male factor [with sperm count <20×106/ml, normal morphology <30% or progressive motility (grade A+B) <40% before sperm preparation] in 21%, ovulatory dysfunction in 9%, endometriosis in 6% and tubal abnormalities in 4% of the couples. Infertility was primary in 58% of cases. The mean age (SD) of the female partners was 31.8 (4.5) years, ranging from 20 to 42 years, and the duration of infertility was 3.4 (2.4) years, ranging from 1 to 13 years. Data on 111 IUI pregnancies and births (92 singleton, 16 twin and three triplet births) was found in the Finnish Medical Birth Register (MBR), but information on 14 cases was missing: one woman had emigrated, and 13 women gave birth in the latter half of the year 1997; therefore, their data were not available at the time of data collection. Thus, the study involved 111 pregnancies and deliveries and 133 newborns. The MBR, which was the main data source of the study, is a nationwide register, which includes information on maternal background, pregnancy, delivery and perinatal outcome. The MBR is linked to the Central Population Register (live births) and Cause-of-Death Register (perinatal deaths), and its data quality is high for most of the variables (Gissler et al., 1995). The studied factors were the total number of antenatal care visits, intensity of use of antenatal care, visits to outpatient clinics, gestational age at birth, pregnancy and delivery complications, mother's hospitalization, mode of delivery, infant's outcome and need for intensive care. Intensity of use of antenatal care was measured by means of a relative index (Gissler et al., 1995). This was calculated by dividing the actual number of visits by the gestation-adjusted recommendation given by the Ministry of Health and Social Affairs (12 visits for a pregnancy of average gestational length). A score of 1.0 indicates the norm. As controls, two different groups were chosen from the Finnish MBR. In both control groups three controls for each IUI case were selected. One group included women with birth after IVF (IVF group, n = 333), and the other consisted of women with non-assisted pregnancy and birth (spontaneous group, n = 333). Each control group involved 399 infants. The controls were matched according to year of delivery, number of fetuses, number of previous deliveries, maternal age, residence of mothers (12 counties), maternal smoking and socio-economic class of the mothers defined by maternal occupation (upper white-collar, low white-collar, blue-collar workers and others; Gissler et al., 1998). Detailed data on matching are shown in Table I. Because of the high number of multiple births, we were not able to match the controls with the cases for all items. Differences between cases and controls were statistically significant as regards residence and socio-economic class. Comparisons between groups and statistical analysis were performed using SAS computer programs, and t- and χ2-tests. The chosen level of significance was P < 0.05. Results Generally the use of antenatal services was high in all groups. However, the IUI group used significantly fewer health care services than the IVF controls (Table II). This difference was more marked in singleton pregnancies in respect to all studied parameters: the total number of antenatal visits (P < 0.01), intensity of use of antenatal care (P < 0.001) and ambulatory visits (P < 0.001). Surprisingly, the mothers with multiple pregnancy in the IUI group had significantly more ambulatory visits than did the non-assisted and IVF controls (P < 0.05 and 0.01 respectively). Prenatal karyotyping was carried out by chorionic villus sampling in one IUI case (1%) and amniocentesis in eight IUI cases (7%), with normal results. In the spontaneous group, chorionic villus sampling was performed in 1% and amniocentesis in 10% of the mothers. The corresponding figures were 1 and 8% respectively, in the IVF group. Maternal hospitalization during pregnancy occurred frequently in all groups. In the IUI group, 28% of women with singleton pregnancy and 74% with multiple pregnancy were hospitalized. There were no statistically significant differences between cases and controls as regards the reasons for hospitalization (haemorrhage, hypertension, threatened premature delivery). Furthermore, one-third of all IUI mothers were in hospital 2 days before delivery. The IVF and spontaneous groups were similar to the IUI group. The Caesarean section rate was high in the IUI group: 25% in singleton and 58% in multiple pregnancies. Approximately half of the Caesarean sections were classified as emergency. The other groups were similar. The incidence of term breech presentation was 1% in IUI singletons and 21% in IUI multiples, and pregnancy complications as placenta praevia, placental abruption, eclampsia or insulin-treated diabetes mellitus of the mother occurred rarely in each group. The data of pregnancy outcome are shown in Table III. The mean gestational age of IUI newborns was 39.5 weeks in singletons and 36.0 weeks in multiples and the incidence of preterm birth (<37 weeks gestation) was 8.7 and 36.8% respectively. There were no differences between IUI births and controls. The mean birth weight of IUI singletons was comparable to that of IVF singletons, but was significantly lower than that of the spontaneous group. However, the latter was explained by shorter gestational age in IUI singletons. When adjusted for gestational age, the difference in mean birth weight between IUI and spontaneous singletons became statistically insignificant, 3311 g versus 3404 g, respectively. Social class, treatment modality and aetiology of infertility did not explain the remaining difference. The proportion of infants with low birth weight (<2500 g) was similar in all groups. Low Apgar scores (0–6 at 1 min) were found in 8.3% of IUI infants, and 12.8% were treated in a newborn surveillance unit and 14.3% in an intensive care unit. One major malformation (Potter's syndrome) and two perinatal deaths occurred in the IUI group. In addition to the infant with lethal Potter's syndrome, one triplet with severe growth retardation for an unknown reason died in utero at 30 weeks of gestation. In both control groups, reliable data on congenital malformations were not available. The number of complications among newborns did not differ between groups. More detailed data on the perinatal outcome are presented in Table IV. Discussion In the present study, we evaluated the obstetric and perinatal outcome of a cohort of women who became pregnant after IUI with the partner's spermatozoa. To exclude the effects of individual background factors and to compare two different infertility treatment methods, we matched the IUI parturients with controls who conceived either spontaneously or after IVF. Data on the controls were obtained from the Finnish MBR, whose data quality is high (Gissler et al., 1995). The high number of multiple pregnancies made matching difficult, especially in respect to mothers' residence and social status. This significant difference between cases and controls could be a possible source of bias. However, social status has been found to be a minor risk factor as regards adverse perinatal outcome in recent Finnish studies (Sipilä et al., 1994; Gissler et al., 1998). The use of maternity care services in Finland is voluntary and free of charge and 99.8% of parturients used these services in 1986 (Sipilä et al., 1994), and 99.7% in 1995 (Gissler et al., 1996). In our study, most IUI parturients were primiparous (81%), the mean number of previous deliveries was low (0.24) and the mean age of the parturients was high (32 years). These values differed clearly from the average national figures (39%, 1.1 and 30 years respectively) for all Finnish parturients in 1995 (Gissler et al., 1996), but were comparable to those associated with assisted reproduction technology pregnancies (Wennerholm et al., 1996, 1997; Dhont et al., 1997; Reubinoff et al., 1997). In addition, the number of multiple gestations (17%) was much higher in the study population than in general (1.4%; Gissler et al., 1996), but slightly lower than in IVF pregnancies (25%; Gissler et al., 1995). Overall, the intensity of use of antenatal care was high in all groups. It did not differ in multiple pregnancies or between IUI and spontaneous singletons, but was significantly higher in IVF singletons compared with IUI singletons. An explanation for the frequent need of antenatal care in all groups might be the high number of mothers of advanced age, primiparity and multiple pregnancy. All these factors have been documented to be predictive of increased obstetric risk and adverse outcome of pregnancy (Hartikainen-Sorri et al., 1990; Chattingius et al., 1992; Sipilä et al., 1994). In addition, the restructuring policy in the maternity health care system in our country might be reflected in the frequent use of maternal care. Generally, a trend towards an increasing number of antenatal care visits has been seen in the last few years in Finland (Gissler et al., 1996). The difference between IUI and IVF singleton pregnancies in respect to the use of antenatal care could be partly explained by inaccurate recommendations concerning the follow-up of IVF pregnancies, based on the results of previous studies (Doyle et al., 1992; Olivennes et al., 1993). In addition, IVF mothers' own desire for close follow-up might increase the intensity of follow-up. The number of pregnancy complications was not increased in the IVF group compared with the IUI group. Optimal and cost-effective follow-up of assisted pregnancies should be based on clear recommendations and should be carried out according to the individual needs of the patient. In total, 36% of IUI, 34% of normally conceiving and 40% of IVF mothers were hospitalized during pregnancy. As expected, the frequency of hospitalization was increased with multiples compared with singletons. The reasons for hospitalization included diagnoses of haemorrhage, hypertension, threatened premature delivery, and other reasons. As regards the distribution of the first three diagnoses, there was no significant difference between the groups. The hospitalization rates of our study and control groups were higher than the average value of 21% reported in Finnish Perinatal Statistics 1995 (Gissler et al., 1996). Pregnancies after IUI did not carry any increased risk of placenta praevia, placental abruption or eclampsia, which has also been shown to be the case in IVF pregnancies (Reubinoff et al., 1997; Wennerholm et al., 1997). Because there was no difference between spontaneous and other pregnancies, it can be suggested that the assisted reproductive techniques as such do not influence the complication risk during pregnancy, but that individual patient characteristics and plurality are the most important factors in this respect. There was no significant difference between the IUI, spontaneous and IVF groups in the Caesarean section rate, which was 25% in singleton and 58% in multiple IUI pregnancies. This is in accordance with recent results (Dhont et al., 1997) reporting no difference between Caesarean section rates of IVF/intracytoplasmic sperm injection (ICSI) and spontaneous pregnancies, but contradictory to some other reports, in which higher Caesarean section rates have been seen among IVF pregnancies (Tanbo et al., 1995; Reubinoff et al., 1997). The present Caesarean section rates were generally higher than average (16%) in Finland (Gissler et al., 1996), the probable reasons again being multiplicity and the mothers' characteristics. In the present study, the mean birth weight of IUI singletons (3285 g) was significantly lower than in the spontaneous group, but there was no difference compared with the IVF group. The difference between the IUI and the spontaneous group was mainly explained by shorter gestational age of IUI singletons, but it could also partly be related to infertility itself (Ghazi et al., 1991; Wang et al., 1994; Sundström et al., 1997; Isaksson et al., 1998). This finding might not be clinically significant, because the incidences of low birth weight and premature delivery did not differ between spontaneous and other pregnancies. The results of studies comparing the birth weight of IVF and naturally conceived infants are somewhat contradictory (Gissler et al., 1995; Reubinoff et al., 1997; Wennerholm et al., 1997). The mean gestational age at delivery was similar among the three groups, and it was comparable to those of some reports evaluating IVF, ICSI and IUI (with donor semen) pregnancies (Wisanto et al., 1995; Dhont et al., 1997; Lansac et al., 1997, Wennerholm et al., 1997). The outcome of newborns was not worse in the IUI or IVF group compared with the spontaneous group in respect to the number of malformations and perinatal mortality. In conclusion, IUI treatment does not adversely influence the outcome of pregnancy or the newborn compared with matched spontaneous and IVF pregnancies. The overall intensity of antenatal care and the hospitalization rate was high in all groups obviously as a result of the high number of multiple pregnancies and the special characteristics of the studied mothers: advanced age and primiparity. The use of antenatal care services in singleton pregnancies was significantly lower in the IUI and spontaneous groups than in the IVF group. Optimal follow-up of assisted pregnancies should be based on the individual characteristics of pregnancies and mothers. On the other hand, to avoid excessive use of maternal health care services, recommendations concerning the follow-up of assisted pregnancies and education of the staff of maternal care units are needed. The main challenge as regards improved outcome of assisted pregnancies is to lower the high incidence of multiple gestation. Table I. Matching criteria and maternal characteristics of the three pregnancy groups   IUI  Spontaneous  IVF  P-value  aFor IUI cases in 1997, controls were sought in 1996 data.  No. of women  111  333  333    Year of newborns' birth (% of total)          1992  12.6  12.6  12.6    1993  11.7  11.7  11.7    1994  18.0  18.0  18.0  1.000  1995  23.4  23.4  23.4    1996–1997a  34.2  34.2  34.2    No. of fetuses (% of total)          1  82.9  82.9  82.9    2  14.4  14.4  14.4  1.000  3  2.7  2.7  2.7    No. of previous deliveries (% of total)          0  81.1  80.2  79.8    1  15.3  16.2  17.4    2  1.8  1.8  1.5  0.991  3+  1.8  1.2  1.8    Mean no. (SD)  0.24 (0.58)  0.25 (0.58)  0.24 (0.53)    Maternal age (years) (% of total)          20–24  7.2  7.2  5.7    25–29  30.6  32.1  31.5    30–34  39.6  38.1  39.3  0.998  35–39  18.0  18.0  19.2    40–44  4.5  4.5  4.2    Mean age (SD)  31.83 (4.53)  31.77 (4.54)  31.92 (4.52)    County of residence (% of total)          Uusimaa  2.7  3.9  16.5    Oulu  70.3  60.4  28.5    Lappi  16.2  18.9  7.2  0.001  Other 9 counties  10.8  16.8  47.8    Smoking during pregnancy (% of total)  12.6  11.7  12.3  0.957  Mother's socio-economic status (% of total)          Upper white-collar  24.3  24.3  20.1    Lower white-collar  47.8  48.4  53.5    Blue-collar  4.5  11.1  12.9    Farmer, entrepreneur  7.2  9.0  6.6  0.001  Student  3.6  2.4  5.1    Other or missing  12.6  4.8  1.8      IUI  Spontaneous  IVF  P-value  aFor IUI cases in 1997, controls were sought in 1996 data.  No. of women  111  333  333    Year of newborns' birth (% of total)          1992  12.6  12.6  12.6    1993  11.7  11.7  11.7    1994  18.0  18.0  18.0  1.000  1995  23.4  23.4  23.4    1996–1997a  34.2  34.2  34.2    No. of fetuses (% of total)          1  82.9  82.9  82.9    2  14.4  14.4  14.4  1.000  3  2.7  2.7  2.7    No. of previous deliveries (% of total)          0  81.1  80.2  79.8    1  15.3  16.2  17.4    2  1.8  1.8  1.5  0.991  3+  1.8  1.2  1.8    Mean no. (SD)  0.24 (0.58)  0.25 (0.58)  0.24 (0.53)    Maternal age (years) (% of total)          20–24  7.2  7.2  5.7    25–29  30.6  32.1  31.5    30–34  39.6  38.1  39.3  0.998  35–39  18.0  18.0  19.2    40–44  4.5  4.5  4.2    Mean age (SD)  31.83 (4.53)  31.77 (4.54)  31.92 (4.52)    County of residence (% of total)          Uusimaa  2.7  3.9  16.5    Oulu  70.3  60.4  28.5    Lappi  16.2  18.9  7.2  0.001  Other 9 counties  10.8  16.8  47.8    Smoking during pregnancy (% of total)  12.6  11.7  12.3  0.957  Mother's socio-economic status (% of total)          Upper white-collar  24.3  24.3  20.1    Lower white-collar  47.8  48.4  53.5    Blue-collar  4.5  11.1  12.9    Farmer, entrepreneur  7.2  9.0  6.6  0.001  Student  3.6  2.4  5.1    Other or missing  12.6  4.8  1.8    View Large Table II. Number of antenatal care and ambulatory visits, and intensity of use of antenatal care by plurality   Singletons  Plural births  Total    IUI  Spont  IVF  IUI  Spont  IVF  IUI  Spont  IVF  a,b,c Significantly different from corresponding value for IUI pregnancies; P < 0.05; 0.01; 0.001 respectively.  Spont = spontaneous.  No. of women  92  276  276  19  57  57  111  333  333  Mean no. of antenatal visits  16.2  15.8  18.1b  17.8  19.4  17.2  16.6  16.6  18.0 a  (SD)  (4.8)  (1.4)  (6.1)  (5.3)  (10.6)  (5.7)  (4.9)  (6.6)   (6.2)  Intensity of antenatal care  1.5  1.4  1.7c  2.1  2.4  2.2  1.6  1.6  1.8 b  (SD)  (0.4)  (0.5)  (0.5)  (0.4)  (1.3)  (0.6)  (0.5)  (0.8)  (0.6)  (1.00 = Norm)                    Mean no. of ambulatory visits  2.4  2.5  3.8c  8.4  6.8 a  6.0 b  3.4  3.2  4.2 a  (SD)  (2.4)  (2.4)  (2.6)  (3.0)  (2.5)  (2.8)  (3.3)  (2.9)  (2.8)    Singletons  Plural births  Total    IUI  Spont  IVF  IUI  Spont  IVF  IUI  Spont  IVF  a,b,c Significantly different from corresponding value for IUI pregnancies; P < 0.05; 0.01; 0.001 respectively.  Spont = spontaneous.  No. of women  92  276  276  19  57  57  111  333  333  Mean no. of antenatal visits  16.2  15.8  18.1b  17.8  19.4  17.2  16.6  16.6  18.0 a  (SD)  (4.8)  (1.4)  (6.1)  (5.3)  (10.6)  (5.7)  (4.9)  (6.6)   (6.2)  Intensity of antenatal care  1.5  1.4  1.7c  2.1  2.4  2.2  1.6  1.6  1.8 b  (SD)  (0.4)  (0.5)  (0.5)  (0.4)  (1.3)  (0.6)  (0.5)  (0.8)  (0.6)  (1.00 = Norm)                    Mean no. of ambulatory visits  2.4  2.5  3.8c  8.4  6.8 a  6.0 b  3.4  3.2  4.2 a  (SD)  (2.4)  (2.4)  (2.6)  (3.0)  (2.5)  (2.8)  (3.3)  (2.9)  (2.8)  View Large Table III. Obstetric outcome by plurality (%)   Singletons  Plural births  Total    IUI  Spont  IVF  IUI  Spont  IVF  IUI  Spont  IVF  Spont = spontaneous.  No. of women  92  276  276  19  57  57  111  333  333  Maternal hospitalization                    During pregnancy  28.3  27.9  34.1  73.7  61.4  70.2  36.0  33.6  40.2  Two days before delivery  22.8  22.8  22.5  63.2  47.4  59.7  29.7  27.0  28.8  Induction of delivery  22.8  21.0  19.2  26.3  14.0  22.8  23.4  19.8  19.8  Caesarean section  25.0  25.0  25.4  57.9  61.4  64.9  30.6  31.2  32.1  Emergency  12.0  15.9  11.2  36.8  36.8  31.6  16.2  19.5  14.7  Elective  13.0  9.1  14.1  21.0  24.6  33.3  14.4  11.7  17.4  Breech presentation  1.1  3.3  5.1  21.1  10.5  22.8  4.5  4.5  8.1  Placenta praevia  0.0  0.0  0.7  0.0  0.0  0.0  0.0  0.0  0.6  Placental abruption  0.0  0.4  0.7  0.0  0.0  0.0  0.0  0.3  0.6  Eclampsia  1.1  0.7  0.4  0.0  0.0  0.0  0.9  0.6  0.3  Diabetes mellitus (insulin-treated)  1.1  1.8  0.7  0.0  3.5  0.0  0.9  2.1  0.6    Singletons  Plural births  Total    IUI  Spont  IVF  IUI  Spont  IVF  IUI  Spont  IVF  Spont = spontaneous.  No. of women  92  276  276  19  57  57  111  333  333  Maternal hospitalization                    During pregnancy  28.3  27.9  34.1  73.7  61.4  70.2  36.0  33.6  40.2  Two days before delivery  22.8  22.8  22.5  63.2  47.4  59.7  29.7  27.0  28.8  Induction of delivery  22.8  21.0  19.2  26.3  14.0  22.8  23.4  19.8  19.8  Caesarean section  25.0  25.0  25.4  57.9  61.4  64.9  30.6  31.2  32.1  Emergency  12.0  15.9  11.2  36.8  36.8  31.6  16.2  19.5  14.7  Elective  13.0  9.1  14.1  21.0  24.6  33.3  14.4  11.7  17.4  Breech presentation  1.1  3.3  5.1  21.1  10.5  22.8  4.5  4.5  8.1  Placenta praevia  0.0  0.0  0.7  0.0  0.0  0.0  0.0  0.0  0.6  Placental abruption  0.0  0.4  0.7  0.0  0.0  0.0  0.0  0.3  0.6  Eclampsia  1.1  0.7  0.4  0.0  0.0  0.0  0.9  0.6  0.3  Diabetes mellitus (insulin-treated)  1.1  1.8  0.7  0.0  3.5  0.0  0.9  2.1  0.6  View Large Table IV. Perinatal outcome of newborns by plurality   Singletons  Plural births  Total    IUI  Spont  IVF  IUI  Spont  IVF  IUI  Spont  IVF  aSignificantly different from corresponding value for IUI pregnancies; P < 0.05.  Spont = spontaneous.  No. of newborns  92  276  276  41  123  123  133  399  399  Mean gestation length (weeks)  39.5  39.8  39.4  36.0  35.6  35.4  38.6  38.7  38.3  (SD)  (1.8)  (1.8)  (2.2)  (2.8)  (2.7)  (3.3)  (2.6)  (2.8)  (3.1)  <37 weeks (%)  8.7  5.1  7.6  36.8  47.4  57.9  13.5  12.3  16.2  Mean birth weight (g)  3285  3448a  3363  2449  2298  2369  3064  3145  3101  (SD)  (575)  (600)  (611)  (678)  (548)  (648)  (706)  (775)  (760)  <2500 g (%)  8.7  6.2  6.9  46.3  56.9  52.0  20.3  21.8  20.8  1 min Apgar score 0–6 (%)  6.5  5.4  6.9  12.0  13.0  15.5  8.3  7.8  8.3  Treatment in newborn surveillance unit (%)  4.4  6.2  4.7  31.7  27.6  34.2  12.8  12.8  13.8  Treatment in intensive care unit (%)  2.2  6.5  4.4  41.4  30.9  32.5  14.3  14.0  3.0  In hospital 7 days after birth (%)  13.0  14.9  9.8  55.8  58.5  63.4  26.3  28.3  26.3  Respiratory distress (%)  0.0  0.4  0.0  4.9  4.1  3.3  1.5  1.5  1.0  Respiratory treatment (%)  3.3  1.8  1.5  4.9  16.3  8.1  3.8  6.3  3.5  Asphyxia (%)  5.4  4.4  3.6  15.8  3.5  3.5  7.2  4.2  3.6  Perinatal mortality (‰)   10.9  7.2  7.2  24.4  8.13  24.4  15.0  7.5  12.5    Singletons  Plural births  Total    IUI  Spont  IVF  IUI  Spont  IVF  IUI  Spont  IVF  aSignificantly different from corresponding value for IUI pregnancies; P < 0.05.  Spont = spontaneous.  No. of newborns  92  276  276  41  123  123  133  399  399  Mean gestation length (weeks)  39.5  39.8  39.4  36.0  35.6  35.4  38.6  38.7  38.3  (SD)  (1.8)  (1.8)  (2.2)  (2.8)  (2.7)  (3.3)  (2.6)  (2.8)  (3.1)  <37 weeks (%)  8.7  5.1  7.6  36.8  47.4  57.9  13.5  12.3  16.2  Mean birth weight (g)  3285  3448a  3363  2449  2298  2369  3064  3145  3101  (SD)  (575)  (600)  (611)  (678)  (548)  (648)  (706)  (775)  (760)  <2500 g (%)  8.7  6.2  6.9  46.3  56.9  52.0  20.3  21.8  20.8  1 min Apgar score 0–6 (%)  6.5  5.4  6.9  12.0  13.0  15.5  8.3  7.8  8.3  Treatment in newborn surveillance unit (%)  4.4  6.2  4.7  31.7  27.6  34.2  12.8  12.8  13.8  Treatment in intensive care unit (%)  2.2  6.5  4.4  41.4  30.9  32.5  14.3  14.0  3.0  In hospital 7 days after birth (%)  13.0  14.9  9.8  55.8  58.5  63.4  26.3  28.3  26.3  Respiratory distress (%)  0.0  0.4  0.0  4.9  4.1  3.3  1.5  1.5  1.0  Respiratory treatment (%)  3.3  1.8  1.5  4.9  16.3  8.1  3.8  6.3  3.5  Asphyxia (%)  5.4  4.4  3.6  15.8  3.5  3.5  7.2  4.2  3.6  Perinatal mortality (‰)   10.9  7.2  7.2  24.4  8.13  24.4  15.0  7.5  12.5  View Large 4 To whom correspondence should be addressed References Brzechffa, P.R., Daneshmand S. and Buyalos, R.P. ( 1998) Sequential clomiphene citrate and human menopausal gonadotrophin with intrauterine insemination: the effect of patient age on clinical outcome. Hum. Reprod.  , 13, 2110–2114. Google Scholar Chattingius,S., Forman,M.R., Berendes,H.N. et al. ( 1992) Delayed childbearing and risk of adverse perinatal outcome. A population-based Study. JAMA  , 268, 886–890. Google Scholar Dawood, M.Y. ( 1996) In vitro fertilization, gamete intrafallopian transfer, and superovulation with intrauterine insemination: efficacy and potential health hazards on babies delivered. Am. J. Obstet. Gynecol.  , 174, 1208–1217. Google Scholar Dhont, M., de Neubourg, F., van der Elst, J. et al. ( 1997) Perinatal outcome of pregnancies after assisted reproduction: a case-control study. Clin. Assist. Reprod.  , 14, 575–580. Google Scholar Dodson, W.C. and Haney, A.F. ( 1991) Controlled ovarian hyperstimulation and intrauterine insemination for treatment of infertility. Fertil. Steril.  , 55, 457–467. 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( 1994) Changes in risk factors for unfavourable pregnancy outcome among singletons over twenty years. Acta Obstet. Gynecol. Scand.  , 73 , 612–618. Google Scholar Söderström-Anttila, V., Tiitinen, A., Foudila, T. and Hovatta, O. ( 1998) Obstetric and perinatal outcome after oocyte donation: comparison with in-vitro fertilization pregnancies. Hum. Reprod.  , 13, 483–490. Google Scholar Sundström, I., Ildgruben, A. and Högberg, U. ( 1997) Treatment-related and treatment-independent deliveries among infertile couples, a long-term follow-up. Acta Obstet. Gynecol. Scand.  , 76, 238–243. Google Scholar Tan, S-L., Doyle, P., Campbell, S. et al. ( 1992) Obstetric outcome of in vitro fertilization pregnancies compared with normally conceived pregnancies. Am. J. Obstet. Gynecol.  , 167, 778–784. Google Scholar Tanbo, T., Dale, P.O., Lunde, O. et al. ( 1995) Obstetric outcome in singleton pregnancies after assisted reproduction. Obstet. Gynecol.  , 86, 188–192. 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Obstetric and perinatal outcome of pregnancies after intrauterine insemination

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Oxford University Press
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© European Society of Human Reproduction and Embryology
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0268-1161
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1460-2350
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10.1093/humrep/14.8.2110
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Abstract

Abstract The main aim of this study was to evaluate the obstetric and perinatal outcome of pregnancies after intrauterine insemination (IUI) with the partner's spermatozoa combined with ovarian stimulation. Information concerning the antenatal care and obstetric and perinatal outcome of IUI pregnancies (n = 111), spontaneous (n = 333) and in-vitro fertilization (IVF) (n = 333) was obtained from the Finnish Medical Birth Register (MBR). The multiple birth rate in the IUI group was 17% (19/111). Significantly less antenatal care was required by the IUI group than the IVF group. The frequency of Caesarean section was 25% for IUI singletons and 58% for IUI multiples, similar to the other groups. The mean (SD) gestational age for IUI singletons at birth was 39.5 (1.8) weeks, with a mean birth weight of 3285 (575) g, compared with 3448 (600) g in non-assisted singletons (P < 0.05). For IUI multiples the mean gestational age at birth was 36.0 (2.8) weeks and the mean birth weight was 2449 (678) g. The incidence of preterm birth, low birth weight or low Apgar scores and the need for neonatal care were similar in all groups. One case of major malformation and two perinatal deaths were recorded in the IUI group. In conclusion, IUI treatment did not appear to increase obstetric or perinatal risks compared with matched spontaneous or IVF pregnancies. Most problems were associated with patient characteristics and multiple pregnancy. Reduction of the high incidence of multiple pregnancies after assisted reproductive technology is essential to improve its outcome. antenatal care, intrauterine insemination, in-vitro fertilization, obstetric outcome, perinatal outcome Introduction The widespread use of assisted reproductive technology has raised a question about the safety for newborns and mothers. An increased frequency of preterm delivery and low birth weight and a high Caesarean section rate has been found in previous studies on the obstetric outcome of pregnancies after in-vitro fertilization (IVF) compared with natural pregnancies (Doyle et al., 1992; Tan et al., 1992; Gissler et al., 1995; Dawood et al., 1996). The risk of haemorrhage and pregnancy-induced hypertension has been found to be high in pregnancies after assisted reproduction technologies, including oocyte recipients (Tan et al., 1992; Tanbo et al., 1995; Söderström-Anttila et al., 1998). Overall, the high proportion of multiple pregnancies after assisted reproduction technologies increases the rate of obstetric and perinatal complications (Tan et al., 1992; Gissler et al., 1995; Wisanto et al., 1995). However, studies with more strictly matched controls have revealed no differences between pregnancies after assisted reproduction or natural conception (Dhont et al., 1997; Minakami et al., 1998), apart from a higher rate of Caesarean section (Reubinoff et al., 1997; Wennerholm et al., 1997). Intrauterine insemination (IUI) combined with ovarian stimulation remains a widely used treatment option for couples with male factor infertility, ovulatory dysfunction, mild endometriosis or unexplained infertility. Intrauterine insemination is a simpler, less invasive and cheaper first-line treatment than IVF for subfertility, resulting in an acceptable pregnancy rate (PR) of 12–20% per cycle (Dodson and Haney, 1991; Nulsen et al., 1993; Nuojua-Huttunen et al., 1997). The multiple PR varies from 7 to 18% (Nulsen et al., 1993; Brzechffa et al., 1998). Although information concerning the outcome of pregnancies and newborns after infertility treatment is essential, so far, the results of studies of pregnancies after IUI with partner's spermatozoa have not been published. In the present study, we evaluated the obstetric and perinatal outcome of pregnancies after IUI with the partner's spermatozoa. The results were compared with those of matched controls of spontaneous and IVF pregnancies. Materials and methods In total, 125 pregnancies ending in birth (>22 weeks of gestation) were achieved after IUI treatment using the partner's spermatozoa, between March 1991 and December 1996 at the Infertility Clinic of the Family Federation of Finland, Oulu. In all cases, ovarian stimulation was combined with IUI and the most commonly used stimulation protocols were clomiphene citrate (CC) alone (11%) or combined with gonadotrophins (73%). In the remaining cycles, gonadotrophins alone or with gonadotrophin-releasing hormone agonist were used. The indication for IUI treatment was unexplained infertility (where history, physical examination, semen analysis, laboratory assessment of ovulation and tubal patency were normal) in 60%, male factor [with sperm count <20×106/ml, normal morphology <30% or progressive motility (grade A+B) <40% before sperm preparation] in 21%, ovulatory dysfunction in 9%, endometriosis in 6% and tubal abnormalities in 4% of the couples. Infertility was primary in 58% of cases. The mean age (SD) of the female partners was 31.8 (4.5) years, ranging from 20 to 42 years, and the duration of infertility was 3.4 (2.4) years, ranging from 1 to 13 years. Data on 111 IUI pregnancies and births (92 singleton, 16 twin and three triplet births) was found in the Finnish Medical Birth Register (MBR), but information on 14 cases was missing: one woman had emigrated, and 13 women gave birth in the latter half of the year 1997; therefore, their data were not available at the time of data collection. Thus, the study involved 111 pregnancies and deliveries and 133 newborns. The MBR, which was the main data source of the study, is a nationwide register, which includes information on maternal background, pregnancy, delivery and perinatal outcome. The MBR is linked to the Central Population Register (live births) and Cause-of-Death Register (perinatal deaths), and its data quality is high for most of the variables (Gissler et al., 1995). The studied factors were the total number of antenatal care visits, intensity of use of antenatal care, visits to outpatient clinics, gestational age at birth, pregnancy and delivery complications, mother's hospitalization, mode of delivery, infant's outcome and need for intensive care. Intensity of use of antenatal care was measured by means of a relative index (Gissler et al., 1995). This was calculated by dividing the actual number of visits by the gestation-adjusted recommendation given by the Ministry of Health and Social Affairs (12 visits for a pregnancy of average gestational length). A score of 1.0 indicates the norm. As controls, two different groups were chosen from the Finnish MBR. In both control groups three controls for each IUI case were selected. One group included women with birth after IVF (IVF group, n = 333), and the other consisted of women with non-assisted pregnancy and birth (spontaneous group, n = 333). Each control group involved 399 infants. The controls were matched according to year of delivery, number of fetuses, number of previous deliveries, maternal age, residence of mothers (12 counties), maternal smoking and socio-economic class of the mothers defined by maternal occupation (upper white-collar, low white-collar, blue-collar workers and others; Gissler et al., 1998). Detailed data on matching are shown in Table I. Because of the high number of multiple births, we were not able to match the controls with the cases for all items. Differences between cases and controls were statistically significant as regards residence and socio-economic class. Comparisons between groups and statistical analysis were performed using SAS computer programs, and t- and χ2-tests. The chosen level of significance was P < 0.05. Results Generally the use of antenatal services was high in all groups. However, the IUI group used significantly fewer health care services than the IVF controls (Table II). This difference was more marked in singleton pregnancies in respect to all studied parameters: the total number of antenatal visits (P < 0.01), intensity of use of antenatal care (P < 0.001) and ambulatory visits (P < 0.001). Surprisingly, the mothers with multiple pregnancy in the IUI group had significantly more ambulatory visits than did the non-assisted and IVF controls (P < 0.05 and 0.01 respectively). Prenatal karyotyping was carried out by chorionic villus sampling in one IUI case (1%) and amniocentesis in eight IUI cases (7%), with normal results. In the spontaneous group, chorionic villus sampling was performed in 1% and amniocentesis in 10% of the mothers. The corresponding figures were 1 and 8% respectively, in the IVF group. Maternal hospitalization during pregnancy occurred frequently in all groups. In the IUI group, 28% of women with singleton pregnancy and 74% with multiple pregnancy were hospitalized. There were no statistically significant differences between cases and controls as regards the reasons for hospitalization (haemorrhage, hypertension, threatened premature delivery). Furthermore, one-third of all IUI mothers were in hospital 2 days before delivery. The IVF and spontaneous groups were similar to the IUI group. The Caesarean section rate was high in the IUI group: 25% in singleton and 58% in multiple pregnancies. Approximately half of the Caesarean sections were classified as emergency. The other groups were similar. The incidence of term breech presentation was 1% in IUI singletons and 21% in IUI multiples, and pregnancy complications as placenta praevia, placental abruption, eclampsia or insulin-treated diabetes mellitus of the mother occurred rarely in each group. The data of pregnancy outcome are shown in Table III. The mean gestational age of IUI newborns was 39.5 weeks in singletons and 36.0 weeks in multiples and the incidence of preterm birth (<37 weeks gestation) was 8.7 and 36.8% respectively. There were no differences between IUI births and controls. The mean birth weight of IUI singletons was comparable to that of IVF singletons, but was significantly lower than that of the spontaneous group. However, the latter was explained by shorter gestational age in IUI singletons. When adjusted for gestational age, the difference in mean birth weight between IUI and spontaneous singletons became statistically insignificant, 3311 g versus 3404 g, respectively. Social class, treatment modality and aetiology of infertility did not explain the remaining difference. The proportion of infants with low birth weight (<2500 g) was similar in all groups. Low Apgar scores (0–6 at 1 min) were found in 8.3% of IUI infants, and 12.8% were treated in a newborn surveillance unit and 14.3% in an intensive care unit. One major malformation (Potter's syndrome) and two perinatal deaths occurred in the IUI group. In addition to the infant with lethal Potter's syndrome, one triplet with severe growth retardation for an unknown reason died in utero at 30 weeks of gestation. In both control groups, reliable data on congenital malformations were not available. The number of complications among newborns did not differ between groups. More detailed data on the perinatal outcome are presented in Table IV. Discussion In the present study, we evaluated the obstetric and perinatal outcome of a cohort of women who became pregnant after IUI with the partner's spermatozoa. To exclude the effects of individual background factors and to compare two different infertility treatment methods, we matched the IUI parturients with controls who conceived either spontaneously or after IVF. Data on the controls were obtained from the Finnish MBR, whose data quality is high (Gissler et al., 1995). The high number of multiple pregnancies made matching difficult, especially in respect to mothers' residence and social status. This significant difference between cases and controls could be a possible source of bias. However, social status has been found to be a minor risk factor as regards adverse perinatal outcome in recent Finnish studies (Sipilä et al., 1994; Gissler et al., 1998). The use of maternity care services in Finland is voluntary and free of charge and 99.8% of parturients used these services in 1986 (Sipilä et al., 1994), and 99.7% in 1995 (Gissler et al., 1996). In our study, most IUI parturients were primiparous (81%), the mean number of previous deliveries was low (0.24) and the mean age of the parturients was high (32 years). These values differed clearly from the average national figures (39%, 1.1 and 30 years respectively) for all Finnish parturients in 1995 (Gissler et al., 1996), but were comparable to those associated with assisted reproduction technology pregnancies (Wennerholm et al., 1996, 1997; Dhont et al., 1997; Reubinoff et al., 1997). In addition, the number of multiple gestations (17%) was much higher in the study population than in general (1.4%; Gissler et al., 1996), but slightly lower than in IVF pregnancies (25%; Gissler et al., 1995). Overall, the intensity of use of antenatal care was high in all groups. It did not differ in multiple pregnancies or between IUI and spontaneous singletons, but was significantly higher in IVF singletons compared with IUI singletons. An explanation for the frequent need of antenatal care in all groups might be the high number of mothers of advanced age, primiparity and multiple pregnancy. All these factors have been documented to be predictive of increased obstetric risk and adverse outcome of pregnancy (Hartikainen-Sorri et al., 1990; Chattingius et al., 1992; Sipilä et al., 1994). In addition, the restructuring policy in the maternity health care system in our country might be reflected in the frequent use of maternal care. Generally, a trend towards an increasing number of antenatal care visits has been seen in the last few years in Finland (Gissler et al., 1996). The difference between IUI and IVF singleton pregnancies in respect to the use of antenatal care could be partly explained by inaccurate recommendations concerning the follow-up of IVF pregnancies, based on the results of previous studies (Doyle et al., 1992; Olivennes et al., 1993). In addition, IVF mothers' own desire for close follow-up might increase the intensity of follow-up. The number of pregnancy complications was not increased in the IVF group compared with the IUI group. Optimal and cost-effective follow-up of assisted pregnancies should be based on clear recommendations and should be carried out according to the individual needs of the patient. In total, 36% of IUI, 34% of normally conceiving and 40% of IVF mothers were hospitalized during pregnancy. As expected, the frequency of hospitalization was increased with multiples compared with singletons. The reasons for hospitalization included diagnoses of haemorrhage, hypertension, threatened premature delivery, and other reasons. As regards the distribution of the first three diagnoses, there was no significant difference between the groups. The hospitalization rates of our study and control groups were higher than the average value of 21% reported in Finnish Perinatal Statistics 1995 (Gissler et al., 1996). Pregnancies after IUI did not carry any increased risk of placenta praevia, placental abruption or eclampsia, which has also been shown to be the case in IVF pregnancies (Reubinoff et al., 1997; Wennerholm et al., 1997). Because there was no difference between spontaneous and other pregnancies, it can be suggested that the assisted reproductive techniques as such do not influence the complication risk during pregnancy, but that individual patient characteristics and plurality are the most important factors in this respect. There was no significant difference between the IUI, spontaneous and IVF groups in the Caesarean section rate, which was 25% in singleton and 58% in multiple IUI pregnancies. This is in accordance with recent results (Dhont et al., 1997) reporting no difference between Caesarean section rates of IVF/intracytoplasmic sperm injection (ICSI) and spontaneous pregnancies, but contradictory to some other reports, in which higher Caesarean section rates have been seen among IVF pregnancies (Tanbo et al., 1995; Reubinoff et al., 1997). The present Caesarean section rates were generally higher than average (16%) in Finland (Gissler et al., 1996), the probable reasons again being multiplicity and the mothers' characteristics. In the present study, the mean birth weight of IUI singletons (3285 g) was significantly lower than in the spontaneous group, but there was no difference compared with the IVF group. The difference between the IUI and the spontaneous group was mainly explained by shorter gestational age of IUI singletons, but it could also partly be related to infertility itself (Ghazi et al., 1991; Wang et al., 1994; Sundström et al., 1997; Isaksson et al., 1998). This finding might not be clinically significant, because the incidences of low birth weight and premature delivery did not differ between spontaneous and other pregnancies. The results of studies comparing the birth weight of IVF and naturally conceived infants are somewhat contradictory (Gissler et al., 1995; Reubinoff et al., 1997; Wennerholm et al., 1997). The mean gestational age at delivery was similar among the three groups, and it was comparable to those of some reports evaluating IVF, ICSI and IUI (with donor semen) pregnancies (Wisanto et al., 1995; Dhont et al., 1997; Lansac et al., 1997, Wennerholm et al., 1997). The outcome of newborns was not worse in the IUI or IVF group compared with the spontaneous group in respect to the number of malformations and perinatal mortality. In conclusion, IUI treatment does not adversely influence the outcome of pregnancy or the newborn compared with matched spontaneous and IVF pregnancies. The overall intensity of antenatal care and the hospitalization rate was high in all groups obviously as a result of the high number of multiple pregnancies and the special characteristics of the studied mothers: advanced age and primiparity. The use of antenatal care services in singleton pregnancies was significantly lower in the IUI and spontaneous groups than in the IVF group. Optimal follow-up of assisted pregnancies should be based on the individual characteristics of pregnancies and mothers. On the other hand, to avoid excessive use of maternal health care services, recommendations concerning the follow-up of assisted pregnancies and education of the staff of maternal care units are needed. The main challenge as regards improved outcome of assisted pregnancies is to lower the high incidence of multiple gestation. Table I. Matching criteria and maternal characteristics of the three pregnancy groups   IUI  Spontaneous  IVF  P-value  aFor IUI cases in 1997, controls were sought in 1996 data.  No. of women  111  333  333    Year of newborns' birth (% of total)          1992  12.6  12.6  12.6    1993  11.7  11.7  11.7    1994  18.0  18.0  18.0  1.000  1995  23.4  23.4  23.4    1996–1997a  34.2  34.2  34.2    No. of fetuses (% of total)          1  82.9  82.9  82.9    2  14.4  14.4  14.4  1.000  3  2.7  2.7  2.7    No. of previous deliveries (% of total)          0  81.1  80.2  79.8    1  15.3  16.2  17.4    2  1.8  1.8  1.5  0.991  3+  1.8  1.2  1.8    Mean no. (SD)  0.24 (0.58)  0.25 (0.58)  0.24 (0.53)    Maternal age (years) (% of total)          20–24  7.2  7.2  5.7    25–29  30.6  32.1  31.5    30–34  39.6  38.1  39.3  0.998  35–39  18.0  18.0  19.2    40–44  4.5  4.5  4.2    Mean age (SD)  31.83 (4.53)  31.77 (4.54)  31.92 (4.52)    County of residence (% of total)          Uusimaa  2.7  3.9  16.5    Oulu  70.3  60.4  28.5    Lappi  16.2  18.9  7.2  0.001  Other 9 counties  10.8  16.8  47.8    Smoking during pregnancy (% of total)  12.6  11.7  12.3  0.957  Mother's socio-economic status (% of total)          Upper white-collar  24.3  24.3  20.1    Lower white-collar  47.8  48.4  53.5    Blue-collar  4.5  11.1  12.9    Farmer, entrepreneur  7.2  9.0  6.6  0.001  Student  3.6  2.4  5.1    Other or missing  12.6  4.8  1.8      IUI  Spontaneous  IVF  P-value  aFor IUI cases in 1997, controls were sought in 1996 data.  No. of women  111  333  333    Year of newborns' birth (% of total)          1992  12.6  12.6  12.6    1993  11.7  11.7  11.7    1994  18.0  18.0  18.0  1.000  1995  23.4  23.4  23.4    1996–1997a  34.2  34.2  34.2    No. of fetuses (% of total)          1  82.9  82.9  82.9    2  14.4  14.4  14.4  1.000  3  2.7  2.7  2.7    No. of previous deliveries (% of total)          0  81.1  80.2  79.8    1  15.3  16.2  17.4    2  1.8  1.8  1.5  0.991  3+  1.8  1.2  1.8    Mean no. (SD)  0.24 (0.58)  0.25 (0.58)  0.24 (0.53)    Maternal age (years) (% of total)          20–24  7.2  7.2  5.7    25–29  30.6  32.1  31.5    30–34  39.6  38.1  39.3  0.998  35–39  18.0  18.0  19.2    40–44  4.5  4.5  4.2    Mean age (SD)  31.83 (4.53)  31.77 (4.54)  31.92 (4.52)    County of residence (% of total)          Uusimaa  2.7  3.9  16.5    Oulu  70.3  60.4  28.5    Lappi  16.2  18.9  7.2  0.001  Other 9 counties  10.8  16.8  47.8    Smoking during pregnancy (% of total)  12.6  11.7  12.3  0.957  Mother's socio-economic status (% of total)          Upper white-collar  24.3  24.3  20.1    Lower white-collar  47.8  48.4  53.5    Blue-collar  4.5  11.1  12.9    Farmer, entrepreneur  7.2  9.0  6.6  0.001  Student  3.6  2.4  5.1    Other or missing  12.6  4.8  1.8    View Large Table II. Number of antenatal care and ambulatory visits, and intensity of use of antenatal care by plurality   Singletons  Plural births  Total    IUI  Spont  IVF  IUI  Spont  IVF  IUI  Spont  IVF  a,b,c Significantly different from corresponding value for IUI pregnancies; P < 0.05; 0.01; 0.001 respectively.  Spont = spontaneous.  No. of women  92  276  276  19  57  57  111  333  333  Mean no. of antenatal visits  16.2  15.8  18.1b  17.8  19.4  17.2  16.6  16.6  18.0 a  (SD)  (4.8)  (1.4)  (6.1)  (5.3)  (10.6)  (5.7)  (4.9)  (6.6)   (6.2)  Intensity of antenatal care  1.5  1.4  1.7c  2.1  2.4  2.2  1.6  1.6  1.8 b  (SD)  (0.4)  (0.5)  (0.5)  (0.4)  (1.3)  (0.6)  (0.5)  (0.8)  (0.6)  (1.00 = Norm)                    Mean no. of ambulatory visits  2.4  2.5  3.8c  8.4  6.8 a  6.0 b  3.4  3.2  4.2 a  (SD)  (2.4)  (2.4)  (2.6)  (3.0)  (2.5)  (2.8)  (3.3)  (2.9)  (2.8)    Singletons  Plural births  Total    IUI  Spont  IVF  IUI  Spont  IVF  IUI  Spont  IVF  a,b,c Significantly different from corresponding value for IUI pregnancies; P < 0.05; 0.01; 0.001 respectively.  Spont = spontaneous.  No. of women  92  276  276  19  57  57  111  333  333  Mean no. of antenatal visits  16.2  15.8  18.1b  17.8  19.4  17.2  16.6  16.6  18.0 a  (SD)  (4.8)  (1.4)  (6.1)  (5.3)  (10.6)  (5.7)  (4.9)  (6.6)   (6.2)  Intensity of antenatal care  1.5  1.4  1.7c  2.1  2.4  2.2  1.6  1.6  1.8 b  (SD)  (0.4)  (0.5)  (0.5)  (0.4)  (1.3)  (0.6)  (0.5)  (0.8)  (0.6)  (1.00 = Norm)                    Mean no. of ambulatory visits  2.4  2.5  3.8c  8.4  6.8 a  6.0 b  3.4  3.2  4.2 a  (SD)  (2.4)  (2.4)  (2.6)  (3.0)  (2.5)  (2.8)  (3.3)  (2.9)  (2.8)  View Large Table III. Obstetric outcome by plurality (%)   Singletons  Plural births  Total    IUI  Spont  IVF  IUI  Spont  IVF  IUI  Spont  IVF  Spont = spontaneous.  No. of women  92  276  276  19  57  57  111  333  333  Maternal hospitalization                    During pregnancy  28.3  27.9  34.1  73.7  61.4  70.2  36.0  33.6  40.2  Two days before delivery  22.8  22.8  22.5  63.2  47.4  59.7  29.7  27.0  28.8  Induction of delivery  22.8  21.0  19.2  26.3  14.0  22.8  23.4  19.8  19.8  Caesarean section  25.0  25.0  25.4  57.9  61.4  64.9  30.6  31.2  32.1  Emergency  12.0  15.9  11.2  36.8  36.8  31.6  16.2  19.5  14.7  Elective  13.0  9.1  14.1  21.0  24.6  33.3  14.4  11.7  17.4  Breech presentation  1.1  3.3  5.1  21.1  10.5  22.8  4.5  4.5  8.1  Placenta praevia  0.0  0.0  0.7  0.0  0.0  0.0  0.0  0.0  0.6  Placental abruption  0.0  0.4  0.7  0.0  0.0  0.0  0.0  0.3  0.6  Eclampsia  1.1  0.7  0.4  0.0  0.0  0.0  0.9  0.6  0.3  Diabetes mellitus (insulin-treated)  1.1  1.8  0.7  0.0  3.5  0.0  0.9  2.1  0.6    Singletons  Plural births  Total    IUI  Spont  IVF  IUI  Spont  IVF  IUI  Spont  IVF  Spont = spontaneous.  No. of women  92  276  276  19  57  57  111  333  333  Maternal hospitalization                    During pregnancy  28.3  27.9  34.1  73.7  61.4  70.2  36.0  33.6  40.2  Two days before delivery  22.8  22.8  22.5  63.2  47.4  59.7  29.7  27.0  28.8  Induction of delivery  22.8  21.0  19.2  26.3  14.0  22.8  23.4  19.8  19.8  Caesarean section  25.0  25.0  25.4  57.9  61.4  64.9  30.6  31.2  32.1  Emergency  12.0  15.9  11.2  36.8  36.8  31.6  16.2  19.5  14.7  Elective  13.0  9.1  14.1  21.0  24.6  33.3  14.4  11.7  17.4  Breech presentation  1.1  3.3  5.1  21.1  10.5  22.8  4.5  4.5  8.1  Placenta praevia  0.0  0.0  0.7  0.0  0.0  0.0  0.0  0.0  0.6  Placental abruption  0.0  0.4  0.7  0.0  0.0  0.0  0.0  0.3  0.6  Eclampsia  1.1  0.7  0.4  0.0  0.0  0.0  0.9  0.6  0.3  Diabetes mellitus (insulin-treated)  1.1  1.8  0.7  0.0  3.5  0.0  0.9  2.1  0.6  View Large Table IV. Perinatal outcome of newborns by plurality   Singletons  Plural births  Total    IUI  Spont  IVF  IUI  Spont  IVF  IUI  Spont  IVF  aSignificantly different from corresponding value for IUI pregnancies; P < 0.05.  Spont = spontaneous.  No. of newborns  92  276  276  41  123  123  133  399  399  Mean gestation length (weeks)  39.5  39.8  39.4  36.0  35.6  35.4  38.6  38.7  38.3  (SD)  (1.8)  (1.8)  (2.2)  (2.8)  (2.7)  (3.3)  (2.6)  (2.8)  (3.1)  <37 weeks (%)  8.7  5.1  7.6  36.8  47.4  57.9  13.5  12.3  16.2  Mean birth weight (g)  3285  3448a  3363  2449  2298  2369  3064  3145  3101  (SD)  (575)  (600)  (611)  (678)  (548)  (648)  (706)  (775)  (760)  <2500 g (%)  8.7  6.2  6.9  46.3  56.9  52.0  20.3  21.8  20.8  1 min Apgar score 0–6 (%)  6.5  5.4  6.9  12.0  13.0  15.5  8.3  7.8  8.3  Treatment in newborn surveillance unit (%)  4.4  6.2  4.7  31.7  27.6  34.2  12.8  12.8  13.8  Treatment in intensive care unit (%)  2.2  6.5  4.4  41.4  30.9  32.5  14.3  14.0  3.0  In hospital 7 days after birth (%)  13.0  14.9  9.8  55.8  58.5  63.4  26.3  28.3  26.3  Respiratory distress (%)  0.0  0.4  0.0  4.9  4.1  3.3  1.5  1.5  1.0  Respiratory treatment (%)  3.3  1.8  1.5  4.9  16.3  8.1  3.8  6.3  3.5  Asphyxia (%)  5.4  4.4  3.6  15.8  3.5  3.5  7.2  4.2  3.6  Perinatal mortality (‰)   10.9  7.2  7.2  24.4  8.13  24.4  15.0  7.5  12.5    Singletons  Plural births  Total    IUI  Spont  IVF  IUI  Spont  IVF  IUI  Spont  IVF  aSignificantly different from corresponding value for IUI pregnancies; P < 0.05.  Spont = spontaneous.  No. of newborns  92  276  276  41  123  123  133  399  399  Mean gestation length (weeks)  39.5  39.8  39.4  36.0  35.6  35.4  38.6  38.7  38.3  (SD)  (1.8)  (1.8)  (2.2)  (2.8)  (2.7)  (3.3)  (2.6)  (2.8)  (3.1)  <37 weeks (%)  8.7  5.1  7.6  36.8  47.4  57.9  13.5  12.3  16.2  Mean birth weight (g)  3285  3448a  3363  2449  2298  2369  3064  3145  3101  (SD)  (575)  (600)  (611)  (678)  (548)  (648)  (706)  (775)  (760)  <2500 g (%)  8.7  6.2  6.9  46.3  56.9  52.0  20.3  21.8  20.8  1 min Apgar score 0–6 (%)  6.5  5.4  6.9  12.0  13.0  15.5  8.3  7.8  8.3  Treatment in newborn surveillance unit (%)  4.4  6.2  4.7  31.7  27.6  34.2  12.8  12.8  13.8  Treatment in intensive care unit (%)  2.2  6.5  4.4  41.4  30.9  32.5  14.3  14.0  3.0  In hospital 7 days after birth (%)  13.0  14.9  9.8  55.8  58.5  63.4  26.3  28.3  26.3  Respiratory distress (%)  0.0  0.4  0.0  4.9  4.1  3.3  1.5  1.5  1.0  Respiratory treatment (%)  3.3  1.8  1.5  4.9  16.3  8.1  3.8  6.3  3.5  Asphyxia (%)  5.4  4.4  3.6  15.8  3.5  3.5  7.2  4.2  3.6  Perinatal mortality (‰)   10.9  7.2  7.2  24.4  8.13  24.4  15.0  7.5  12.5  View Large 4 To whom correspondence should be addressed References Brzechffa, P.R., Daneshmand S. and Buyalos, R.P. 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Journal

Human ReproductionOxford University Press

Published: Aug 1, 1999

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