Pregnancy and child outcome after assisted reproduction techniques

The introduction and widespread application of assisted reproduction techniques have raised major concern about the outcome of resulting pregnancies, as well as about the offspring's health. It seems that pregnancies achieved after standard in-vitro fertilization (IVF) bear an increased risk for prematurity and low birth weight. On the other hand, pregnancy outcome of singletons achieved after intracytoplasmic sperm injection (ICSI) and after the transfer of frozen-thawed embryos is similar to that of spontaneously conceived singletons, and pregnancy complications are related only to gestation multiplicity. The incidence of congenital and chromosomal anomalies after standard IVF seems to be similar to that expected in the general population. The prevalence of congenital malformations does not seem to be higher after ICSI. On the other hand, there is a slightly increased risk for transmission of chromosomal aberrations of paternal origin and a higher risk of de novo, mainly sex-chromosomal aberrations. Postnatal growth and development of children born after standard IVF and cryopreservation seem to be within the normal ranges. Growth of ICSI children is also normal while their mental development needs further investigation. Family functioning in assisted reproduction families is better.     

Obstetric outcome among women with unexplained infertility after IVF: a matched case-control study

BACKGROUND: Infertility itself and also assisted reproductive treatment increase the incidence of some obstetric complications. Women with unexplained infertility are reported to be at an increased risk of intrauterine growth restriction during pregnancy, but not for other perinatal complications. METHODS: A matched case-control study was performed on care during pregnancy and delivery, obstetric complications and infant perinatal outcomes of 107 women with unexplained infertility, with 118 clinical pregnancies after IVF or ICSI treatment. These resulted in 90 deliveries; of these, 69 were singleton, 20 twin and one triplet. Two control groups were chosen from the Finnish Medical Birth Register, one group for spontaneous pregnancies (including 445 women and 545 children), matched according to maternal age, parity, year of birth, mother's residence and number of children at birth, and the other group for all pregnancies after IVF, ICSI or frozen embryo transfer treatment (FET) during the study period (including 2377 women and 2853 children). RESULTS: Among singletons, no difference was found in the mean birthweight, and the incidence of low birthweight (<2500 g) was comparable with that of the control groups. No differences were found in gestational duration, major congenital malformations or perinatal mortality among the groups studied. Among singletons in the study group, there were more term breech presentations (10.1%) compared with both spontaneously conceiving women and all IVF women (P < 0.01). The rate of pregnancy-induced hypertension was significantly lower among singletons in the study group (P < 0.05) compared with other IVF singletons. The multiple pregnancy rate was 23.3% in the study group. The obstetric outcome of the IVF twins was similar to both control groups. CONCLUSIONS: The overall obstetric outcome among couples with unexplained infertility treated with IVF was good, with similar outcome compared with spontaneous pregnancies and IVF pregnancies generally.     

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

BACKGROUND: Over a million children have been born from assisted conception worldwide. Newer techniques being introduced appear less and less 'natural', such as intracytoplasmic sperm injection (ICSI), but there is little information on these children beyond the neonatal period. METHODS: 540 ICSI conceived 5-year-old children from five European countries were comprehensively assessed, along with 538 matched naturally conceived children and 437 children conceived with standard IVF. RESULTS: Of the 540 ICSI children examined, 63 (4.2%) had experienced a major congenital malformation. Compared with naturally conceived children, the odds of a major malformation were 2.77 (95% CI 1.41-5.46) for ICSI children and 1.80 (95% CI 0.85-3.81) for IVF children; these estimates were little affected by adjustment for socio-demographic factors. The higher rate observed in the ICSI group was due partially to an excess of malformations in the (boys') urogenital system. In addition, ICSI and IVF children were more likely than naturally conceived children to have had a significant childhood illness, to have had a surgical operation, to require medical therapy and to be admitted to hospital. A detailed physical examination revealed no further substantial differences between the groups, however. CONCLUSIONS: Singleton ICSI and IVF 5-year-olds are more likely to need health care resources than naturally conceived children. Assessment of singleton ICSI and IVF children at 5 years of age was generally reassuring, however, we found that ICSI children presented with more major congenital malformations and both ICSI and IVF children were more likely to need health care resources than naturally conceived children. Ongoing monitoring of these children is therefore required.     

Neonatal data on a cohort of 2889 infants born after ICSI (1991-1999) and of 2995 infants born after IVF (1983-1999)

BACKGROUND: To evaluate the safety of ICSI, this study compared data of IVF and ICSI children by collecting data on neonatal outcome and congenital malformations during pregnancy and at birth. METHODS: The follow-up study included agreement to genetic counselling and eventual prenatal diagnosis, followed by a physical examination of the children after 2 months, after 1 year and after 2 years. 2840 ICSI children (1991-1999) and 2955 IVF children (1983-1999) were liveborn after replacement of fresh embryos. ICSI was carried out using ejaculated, epididymal or testicular sperm. RESULTS: In the two cohorts, similar rates of multiple pregnancies were observed. ICSI and IVF maternal characteristics were comparable for medication taken during pregnancy, pregnancy duration and maternal educational level, whereas maternal age was higher in ICSI and a higher percentage of first pregnancies and first children born was observed in the ICSI mothers. Birthweight, number of neonatal complications, low birthweight, stillbirth rate and perinatal death rate were compared between the ICSI and the IVF groups and were similar for ICSI and IVF. Prematurity was slightly higher in the ICSI children (31.8%) than in the IVF children (29.3%). Very low birthweight was higher in the IVF pregnancies (5.7%) compared with ICSI pregnancies (4.4%). Major malformations (defined as those causing functional impairment or requiring surgical correction), were observed at birth in 3.4% of the ICSI liveborn children and in 3.8% of the IVF children (P = 0.538). Malformation rate in ICSI was not related to sperm origin or sperm quality. The number of stillbirths (born > or =20 weeks of pregnancy) was 1.69% in the ICSI group and 1.31% in the IVF group. Total malformation rate taking into account major malformations in stillborns, in terminations and in liveborns was 4.2% in ICSI and 4.6% in IVF (P = 0.482). CONCLUSIONS: The comparison of ICSI and IVF children taking part in an identical follow-up study did not show any increased risk of major malformations and neonatal complications in the ICSI group.     

A review of ten years experience of ICSI

This review summarizes the introduction of ICSI in the early 1990s as an assisted fertilization procedure in couples with severe male factor infertility, who could not be helped by conventional IVF. As for current practice, the indications for ICSI using fresh or frozen-thawed ejaculated, epididymal or testicular sperm are reviewed as well as some reports on the use of ICSI in non-male infertility. The main steps in an ICSI cycle are well standardized by now; it is rare that ICSI cannot be carried out and the results in terms of fertilization, embryo transfer and clinical pregnancy rate have been consistent for many years, indicating that a substantial number of couples can now have their own genetic child instead of having to use artificial insemination with donor sperm. This review also emphasizes the importance of assessing the risk of ICSI for the children: there is a slight increase in de novo chromosomal abnormalities, the major congenital malformation rate is similar for IVF and ICSI (between 3 and 4%), and at approximately 2 years of age the developmental outcome as assessed by the Bayley scale is similar for IVF and ICSI. Recent publications mention that a few children are affected by diseases caused by imprinting disorders. Future studies are needed to assess the association between assisted reproductive technologies and imprinting disorders. ICSI is frequently used in couples undergoing preimplantation genetic diagnosis. PGD stricto sensu as well as PGD for aneuploidy screening and for Klinefelter patients are reviewed using the ESHRE PGD Consortium data.     

Congenital malformations in 4224 children conceived after IVF

BACKGROUND: The percentage of children born after IVF will continue to increase due to demographic changes such as increasing maternal age and new developments in assisted reproduction techniques. IVF conceptions may carry an increased risk of congenital malformations. METHODS: We compared overall and specific congenital malformation rates calculated for IVF children (n = 4224) and naturally conceived children (n = 314 605), using records from the same Dutch national database for the years 1995 and 1996 and controlling for confounding maternal factors. RESULTS: The overall crude odds ratio (OR) for the risk of any malformation for IVF children compared with naturally conceived children was 1.20 [95% confidence interval (CI): 1.01-1.43]. After correction for differences in maternal age, parity and ethnicity between the IVF and control population the OR was 1.03 (95% CI: 0.86-1.23). The crude OR for IVF children appeared higher for the cardiovascular organ system and for several specific minor congenital malformations. However, these could be chance findings due to comparison of many malformation categories or may result from remaining differences in ascertaining malformations between IVF and naturally conceived children. CONCLUSIONS: The small increase in overall congenital malformations observed in the IVF children appears to be attributable to differences in maternal characteristics and not to any aspect of the IVF procedure.     

Follow-up of children born after ICSI

The comparison of outcome of assisted reproductive technology (ART) children and naturally conceived children may be hampered by the difference in characteristics of the infertile patients such as age and genetic risks. Follow-up studies are further hampered by the type of neonatal surveillance protocol, the number of individuals lost to follow-up, the size of the cohort study, and the lack of standardization, for example to define major anomalies. The limited available data on ICSI fetal karyotypes reveal that, in comparison with a general neonatal population, there is: (i) a slight but significant increase in de-novo sex chromosomal aneuploidy (0.6% instead of 0.2%) and structural autosomal abnormalities (0.4% instead of 0.07%); and (ii) an increased number of inherited (mostly from the infertile father) structural aberrations. Available data indicate that in 8319 liveborn ICSI children, the mean percentage who do not originate from singleton pregnancies was 40% (range 32.6-60.8% according to centre). Most multiples are twins, but there are also 4.4% triplets (in one survey 13.2%). This substantial increase in multiple pregnancies must be considered the most important complication of ART. The different percentages of major and minor congenital malformations cannot be compared, but overall the data in large and reliable surveys does not indicate a higher rate of malformations in ICSI children than in naturally conceived children. To date, only three studies have examined the medical and developmental outcome of ICSI children at 1 and 2 years. These do not reveal obvious problems, but in future further comparison of matched cohorts of children and case-control studies are needed before final conclusions can be drawn.     

Genetic and teratogenic effects of cancer treatments on gametes and embryos

Male and female germ cells vary in their sensitivity to the mutagenic effects of chemotherapy and radiotherapy, depending on their stage of maturation and the agent used. Although sperm DNA damage exists following treatment, no increase in genetic defects or congenital malformations was detected among children conceived to parents who have previously undergone chemotherapy or radiotherapy. The use of assisted reproductive technologies and micromanipulation techniques might increase this risk; hence caution should be exercised. In female cancer patients, miscarriage and congenital malformations are not increased following chemotherapy. However, when IVF and embryo cryopreservation is practised between or shortly after treatment, possible genetic risks to the growing oocytes exist, and hence the babies should be screened. During pregnancy, the potential teratogenic effects of chemotherapy influence the choice and timing of therapy. Termination is usually recommended in the first trimester. Second- and third-trimester exposure does not usually increase the teratogenic risk and cognitive development, but it may increase the risk of poor obstetric outcome and fetal myelosuppression. During the first two weeks after fertilization of the embryo, radiation is lethal but not teratogenic. High doses of radiation during pregnancy induce anomalies, impaired growth and mental retardation, and there may be an increased risk of childhood leukaemia and other tumours in the offspring.     

Comparison of pregnancy outcome after intracytoplasmic sperm injection and in-vitro fertilization

The aim of this study was to compare pregnancy characteristics and perinatal outcome of intracytoplasmic sperm injection (ICSI) pregnancies with pregnancies obtained after in-vitro fertilization (IVF). Retrospectively, 145 ICSI pregnancies were matched with 145 IVF pregnancies using the last menstruation data. The main outcome measures were preclinical and clinical abortions, ectopic pregnancies, multiple gestations, prenatal morbidity, prematurity, Caesarean section, birthweight, perinatal mortality and malformations for singletons, twins and triplets. Although patients were significantly younger (P < 0.001) in ICSI (31 years) than in IVF (33 years), their infertility duration (5 years) was similar. The mean number of transferred embryos (2.7 embryos per transfer) was similar in IVF and ICSI. The rates of preclinical (15%) and clinical abortions (11% in ICSI versus 15% in IVF) were not different. Four ectopic pregnancies were observed in the IVF group and none in the ICSI group. In ICSI, two minor malformations were detected and two therapeutic abortions were performed respectively for polymalformations and suspicion of cystic fibrosis. The rate of congenital malformation was 2.8% in ICSI and 2.2% in IVF. In this last group, one therapeutic abortion for malformation of neural tube was performed and two minor malformations were detected. The rate of aborted embryonic sacs before 16 weeks of gestation was not significantly lower in ICSI compared with IVF (13.7% versus 20%). The rate of multiple gestations was similar in both groups (31% in IVF and 35% in ICSI). The number of Caesarean sections was similar in IVF and in ICSI and was twice as frequent for twins versus singletons. The number of singletons born by Caesarean section was 21% after ICSI and 17% after IVF. Mean birthweights and gestational ages at birth for twins were significantly higher (P < 0.05) in ICSI than in IVF (2488 versus 2281 g and 36.5 versus 35.5 weeks). This difference was not observed for singletons. In conclusion, pregnancy characteristics and perinatal outcome after ICSI showed no increase in the number of pathologies in comparison with IVF.      

'Vanishing embryo syndrome' in IVF/ICSI

BACKGROUND: In a Danish population-based cohort study assessing the risk of cerebral palsy in children born after IVF, we made some interesting observations regarding 'vanishing co-embryos'. METHODS and RESULTS: All live-born children born in Denmark from 1 January 1995 to 31 December 2000 were included in this analysis. The children conceived by IVF/ICSI (9444) were identified through the IVF Register, the children conceived without IVF/ICSI (395 025) were identified through The Danish Medical Birth Register. Main outcome measure was the incidence of cerebral palsy. Within the IVF/ICSI children we found indications of an increased risk of cerebral palsy in those children resulting from pregnancies, where the number of embryos transferred was higher than the number of children born. CONCLUSIONS: The association between vanishing embryo syndrome and incidence of cerebral palsy following IVF requires further investigation in larger, adequately powered, studies.     

Pregnancy: Prospective follow-up study of 55 children born after subzonal insemination and intracytoplasmic sperm injection

In 163 couples referred for assisted fertilization, pregnancywas established by subzonal insemination (SUZI), intracytoplasmicsperm injection (ICSI) or a combination of both techniques.These couples agreed to participate in a prospective study thatincluded a prenatal diagnosis and clinical follow-up of thechildren. No cytogenetic aberrations were observed in 43 childrentested. In 23 pregnancies occurring after SUZI, 15 women gavebirth to 21 children. After replacement of combined SUZI andICSI embryos, 10 pregnancies resulted in 8 deliveries with 10children. Transfer of ICSI embryos led to 130 pregnancies endingin 20 deliveries with 24 children, with many others still ongoingsuccessfully. In total, 55 children have been examined: 29 boysand 26 girls. One child from a singleton pregnancy presentedmultiple congenital malformations; one twin child presenteda quadriparesis. In this observational study on a limited numberof children, the incidence of major malformations was not differentfrom the incidence in the general population.     

Children conceived using ICSI do not have an increased risk of delayed mental development at 5 years of age

BACKGROUND: Concerns about possible adverse outcomes for children conceived using ICSI were highlighted in 1998 when 1-year-old ICSI children were found to be at increased risk (relative risk = 9.2) of delayed mental development compared with children conceived naturally or using IVF. As the findings were biologically plausible, it was considered important to reassess child development when a more accurate measure of long-term cognitive ability could be obtained. METHODS: The mental development of 97 ICSI, 80 IVF and 110 naturally conceived (NC) children at 5 years of age was assessed using intelligence quotients (IQ) obtained from the Wechsler Preschool and Primary Scales of Intelligence. RESULTS: The mean full-scale IQ was 110 +/- 18 for ICSI, 111 +/- 13 for IVF and 114 +/- 13 for NC children (P = 0.21, non-significant). ICSI children were not at increased risk for delayed (full-scale IQ <85) cognitive development (ICSI 5.2%, IVF 2.5%, NC 0.9%; P = 0.18, non-significant). The only significant independent predictor of below-average full-scale IQ on multivariate analysis was lower maternal education level. CONCLUSIONS: These findings suggest that the genetic influence of parental cognitive ability is more important than the mode of conception in determining the long-term intellectual ability of children conceived using ICSI.     

Seven years of intracytoplasmic sperm injection and follow-up of 1987 subsequent children

Intracytoplasmic sperm injection (ICSI) with ejaculated, epididymal or testicular spermatozoa was first successful in 1992 and has since become the widely accepted treatment for couples with severe male-factor infertility. The outcome of several thousands of ICSI cycles in terms of fertilization, embryo cleavage and implantation is similar to that for conventional in-vitro fertilization in couples with tubal or idiopathic infertility. To evaluate the important issue of safety of the new technique of ICSI, a prospective follow-up study of 1987 children born after ICSI was carried out. The aim was to compile data on karyotypes, congenital malformations, growth parameters and developmental milestones. Parents' agreement to genetic counselling was obtained as well as prenatal diagnosis, followed by a physical examination of the children at 2 months, 1 year and 2 years. Between April 1991 and August 1997, 1699, 91 and 118 children were born after ICSI with ejaculated, epididymal and testicular spermatozoa respectively; 79 children were born from cryopreserved ICSI embryos. In all, 1082 karyotypes were determined by prenatal diagnosis, 18 of which were abnormal and de novo (1.66%) (nine each of autosomal and sex chromosomal aberrations), and 10 karyotypes (0.92%) were inherited structural aberrations. Of these, nine (eight balanced structural aberrations and one unbalanced trisomy 21) were transmitted from the father. Ten pregnancies were terminated after prenatal karyotyping or DNA testing. Forty-six major malformations (2.3%) were observed at birth. Seven malformations, observed by prenatal ultrasound, were terminated. Twenty-one (1.1 %) stillbirths, including four with major malformations, occurred later than 20 weeks of pregnancy. Mean gestational age at birth was 38.7 weeks for singletons, 36.0 weeks for twins and 32.0 weeks for triplets. No specifically higher incidence of malformations was found in any given subgroup.     

Spontaneous abortion in multiple pregnancy: focus on fetal pathology

Multiple pregnancy with its wide array of medical consequences poses an important condition during pregnancy. We performed perinatal autopsy in 49 cases of spontaneous abortion resulting from multiple pregnancies during the study period. Twenty-seven of the 44 twin pregnancies ending in miscarriage were conceived naturally, whereas 17 were conceived through assisted reproductive techniques. Each of the 5 triplet pregnancies ending in miscarriage was conceived through assisted reproductive techniques. There was a positive history of miscarriage in 22.4% of the cases. Monochorial placentation occurred more commonly in multiple pregnancies terminating with miscarriage than in multiple pregnancies without miscarriage. A fetal congenital malformation was found in 8 cases. Three of these cases were conceived through assisted reproductive techniques, and 5 were conceived naturally. Miscarriage was due to intrauterine infection in 36% of the cases. Our study confirms that spontaneous abortion is more common in multiple than in singleton pregnancies. Monochorial placentation predicted a higher fetal morbidity and mortality. In pregnancies where all fetuses were of male gender, miscarriage was more common than in pregnancies where all fetuses were female. Assisted reproductive techniques do not predispose to the development of fetal malformations.     

Risk of cancer in the offspring of women who underwent ovarian stimulation for IVF.

BACKGROUND: Over the past decade attention has been increasingly focused on the long-term health effects of assisted reproductive technologies (ART), such as IVF, in both women and their offspring. To determine the risk of cancer in children conceived by IVF we used a large population-based historical cohort that was initially designed to examine the risk of gynaecological disorders in women who underwent IVF. METHODS: Children were included in the exposed group if they were conceived by IVF or other related fertility techniques (n=9484). The unexposed group consisted of 7532 children whose mothers were diagnosed with subfertility disorders but who were conceived naturally. All cohort members were asked to complete a mailed questionnaire that inquired about reproductive variables and cancer in the offspring (response rate 66.9%). RESULTS: During an average follow-up period of 6.0 years, 16 cancers were observed in the exposed and unexposed group combined, whereas 15.5 were expected [standardized incidence ratio (SIR) = 1.0; 95% confidence interval (95% CI) 0.6-1.7]. A direct comparison between children conceived after ART and naturally conceived children revealed no increased risk for childhood malignancies [risk ratio (RR) = 0.8; 95% CI 0.3-2.3]. CONCLUSIONS: Despite the small numbers of observed cancer cases, these findings demonstrate that children conceived by ART have no greatly increased risk of cancer during childhood compared with the general population and the internal reference group.     

Follow-up studies of children born after frozen sperm donation

The need to assess the health of children born after assisted reproductive technologies (ART) using frozen donor spermatozoa has been a major concern for the last decade. Most available published studies are confusing (since they are retrospective) and refer to small numbers of cases or involve a bias. Two prospective and large population-based studies have been published, one in France and the other in Australia. The general characteristics of children born after ART using frozen spermatozoa was unchanged in comparison with the general population (weight, prematurity, stillbirths, sex ratio). However, the rate of multiple pregnancy was increased, first in artificial insemination with donor semen (AID), where the use of hormonal treatment may be too heavily prescribed, and second in IVF with donor semen (IVF/D) where both the ovulation induction treatments and embryo transfer policy increase the rate of multiple pregnancies. As far as birth defects or chromosomal abnormalities are concerned, no difference has been observed from the general population. Finally, the use of frozen spermatozoa does not seem to affect the health of children conceived by AID or IVF/D. The psychosocial development of such infants is not as well known because of the confidentiality in many countries concerning sperm donation. However, the available information on the psychosocial development of these children up to the age of 8-10 years appears to be reassuring. Larger and longer studies are needed to answer such questions, particularly with regard to adulthood.     

Perinatal outcome of 12,021 singleton and 3108 twin births after non-IVF-assisted reproduction: a cohort study

Perinatal outcome of pregnancies caused by assisted reproduction technique (ART) is substantially worse when compared with pregnancies following natural conception. We investigated the possible risks of non-IVF ART on perinatal health. We conducted a retrospective cohort study with two exposure groups: a study group of pregnancies after controlled ovarian stimulation (COS), with or without artificial insemination (AI), and a naturally conceived comparison group. We used the data from the regional registry of all hospital deliveries in the Dutch-speaking part of Belgium during the period from January 1993 until December 2003 to investigate differences in perinatal outcome of singleton and twin pregnancies. 12 021 singleton and 3108 twin births could be selected. Naturally conceived subjects were matched for maternal age, parity, fetal sex and year of birth. The main outcome measures were duration of pregnancy, birth weight, perinatal morbidity and perinatal mortality. Our overall results showed a significantly higher incidence of prematurity (<32 and <37 weeks), low and very low birth weight, transfer to the neonatal intensive care unit and most neonatal morbidity parameters for COS/AI singletons. Twin pregnancies resulting from COS/AI showed an increased rate of neonatal mortality, assisted ventilation and respiratory distress syndrome. After excluding same-sex twin sets, COS/AI twin pregnancies were at increased risk for extreme prematurity and very low birth weight. In conclusion, COS/AI singleton and twin pregnancies are significantly disadvantaged compared to naturally conceived children.     

Uterine artery Doppler velocimetry and the outcome of pregnancies resulting from ICSI.

BACKGROUND: An increased incidence of pregnancy complications following assisted reproduction has been reported. The use of uterine artery Doppler ultrasound may aid the prediction of such complications. METHODS: Doppler was performed at 18-24 weeks gestation in 114 singleton and 32 twin pregnancies after intracytoplasmic sperm injection (ICSI) and compared with a control group matched for age, parity and plurality. Outcome variables included gestational age at delivery, prematurity, preterm premature rupture of membrane (PPROM), birth weight, birth weight discordance of >20% in twins, small for gestational age (SGA), mode of delivery, development of pre-eclampsia and placental abruption. RESULTS: Compared with the controls, there were no significant differences concerning uterine Doppler parameters, pregnancy complications and the neonatal outcome, either in singleton or in twin pregnancies. According to Doppler results and/or risk factors by medical history, 42% of singleton ICSI and 39% of spontaneous singleton pregnancies were considered as high risk. In singletons, abnormal Doppler findings were associated with pre-eclampsia in 22% and SGA in 26% of ICSI patients, compared with 33 and 21% in controls; in contrast, 0 and 10% in ICSI and 3 and 6% in controls showed these complications but no risk factors respectively. No correlation was found between PPROM, prematurity, the rate of Caesarean section and pathological Doppler results. CONCLUSIONS: Uterine Doppler examination holds the potential to identify patients with an increased risk for developing pregnancy complications. According to our results, this risk is not elevated after ICSI treatment, therefore the decision of offering an intensified antenatal care should be based on the results of Doppler examination or risks by medical history rather than the mode of conception.     

The prevalence of major congenital malformations during two periods of time, 1986-1994 and 1995-2002 in newborns conceived by assisted reproduction technology

Evidence has emerged that assisted reproduction technology (ART) may be associated with an increased risk of congenital malformations, low birth weight, and genetic imprinting disorders. The aim of the study was to determine, the prevalence of major malformations in newborns conceived by standard in vitro fertilization (IVF) in 1986-1994 and newborns conceived by different types of ART procedures in 1995-2002. Data were collected from the IVF Registry and Israel Birth Defects Monitoring System for all infants (live births, stillbirths and terminations of pregnancy) delivered after 20 weeks' gestation who achieved a fetal weight of at least 500 g. The control groups consisted of all spontaneously conceived babies (live births, stillbirths and terminations of pregnancy) born in our center during the same time periods. During the first period, a total of 31,007 babies were born at our center, of whom 278 were conceived by standard IVF. Twenty-six of the IVF infants had major malformations, for a prevalence rate of 9.35%, which was 2.3-fold higher than that in the general population (4.05%). During the second period, 53,208 infants were born, of whom 1632 were conceived by ART. Major malformations were found in 147 ART infants, for a prevalence rate of 9.0%, which was 1.75-fold higher than in the general population (5.18%). Analysis of the clinical characteristics of the ART infants with major malformations showed that 70.3% were born preterm, 76.5% had low birth weight, 58.6 were twins, and 11.7% were triplets. The use of ART procedures increased by a factor of 3.4 in the second period. Two important outcomes of ART were observed: an increased prevalence of major malformations about double the general population in both periods, and a high frequency of adverse clinical characteristics among ART infants with major malformations. Infertile couples should be adequately counseled regarding the real risk of having a child with malformations or a preterm or low birth weight infant.     

Cognitive development of 12 month old Greek infants conceived after ICSI and the effects of the method on their parents

BACKGROUND: ICSI is widely used as a method of assisted reproduction in Greece. Research shows that children conceived after the application of ICSI develop normally. However, Bowen et al. (1998) reported that children conceived after ICSI had lower scores in the Mental Development Index (MDI) of the Bayley Scales of Infant Development compared with infants conceived naturally or by standard IVF treatment. This finding raised concerns about the effects of ICSI on infants' cognitive development. The aim of the present study was twofold. First to compare the cognitive development of Greek infants conceived after ICSI treatment to a control group of infants conceived after IVF treatment and to a further control group conceived naturally (NC). Second, to investigate the psychological effects of ICSI compared to IVF on Greek parents. METHODS: The Bayley Scales of Infant Development were employed to assess cognitive development of infants. A 37 item semi-structured interview was devised to obtain demographic information and to assess and compare the psychological effects of ICSI and IVF on parents. RESULTS: The mental development of infants in all three groups was within the normal range (ICSI 101.4, IVF 95.7, NC 98.9). The differences between the three groups were not statistically significant. The duration of pregnancy and the birthweight differed in the three groups. Furthermore, mothers in the IVF and the ICSI groups experienced anxiety during pregnancy. IVF mothers differed in the mode of delivery and a smaller number of these mothers breastfed their infants. CONCLUSIONS: This study has shown that Greek infants, born after the application of ICSI, have mental and motor scores within the normal range. With regard to the psychological effects, it appears that mothers in the ICSI and IVF groups experience greater anxiety during their pregnancies than those in the NC group.