Embryo reduction of multifetal pregnancies following assisted reproduction treatment: a modification of the transvaginal ultrasound-guided technique

First-trimester transvaginal embryo reduction is an effective alternative for the management of multifetal pregnancy in assisted reproduction. We have modified the transvaginal technique by performing an intracardiac embryo puncture until asystolia is verified, without the injection of any substances. Any aspiration of embryo tissues or amniotic fluid was avoided. A total of 149 multifetal pregnancies was reduced to twins (n = 134) or singletons (n = 15) at early gestational age (7.8 +/- 0.8 weeks). Eleven cases (7.3%) of miscarriage, two cases (1.3%) of chorioamnionitis, and 17 cases (11.4%) of transient spotting were recorded as postoperative complications. Vanishing of one embryo occurred in four cases (3.0%) of those reduced to twins. The baby take-home rate was 89.5% for twins and 80.0% for singletons. Pregnancy outcome was analysed and compared with a control group of women with non-reduced multiple pregnancies. The birth weight of singleton pregnancies after reduction was lower (2929 +/- 160 versus 3291 +/- 422 g; P < 0.02). These studies show that early transvaginal intracardiac embryo puncture is an effective and safe technique.     

Parenting and the psychological development of a representative sample of triplets conceived by assisted reproduction

BACKGROUND: The aim of the study was to examine the quality of parenting and the psychological development of three-year-old children in IVF/ICSI families with triplets. METHODS: Comparisons were carried out between a representative sample of 10 families with triplets and matched groups of 15 families with twins and 30 families with singletons. The families were recruited from Follow-Up, a national organization in France that was established to study children conceived by assisted reproduction. Standardized measures of the mother's psychological well-being (parenting stress, depression and quality of marriage) and standardized measures of the child's psychological development (emotional/behavioural problems and general development) were completed by the mother. RESULTS: Mothers with a multiple birth were found to experience greater difficulties in parenting than mothers of singletons, with no differences between mothers of triplets and mothers of twins. Regarding the children, there were no differences in emotional or behavioural problems between triplets, twins and singletons. However, there were indications of mild delay among triplets and twins in some aspects of language development in comparison with the singleton children. CONCLUSIONS: The birth of triplets or twins does appear to cause difficulties for parents in the early years, however, the children themselves do not seem to experience markedly raised levels of psychological or developmental problems.     

Monozygotic twinning after assisted reproductive techniques: a phenomenon independent of micromanipulation

A 3 year retrospective analysis was conducted of pregnancies achieved after various assisted reproductive treatment modalities in our infertility practice, to calculate and compare the rates of monozygotic twinning (MZT). A total of 731 pregnancies achieved after various assisted reproduction treatments were reviewed. Gonadotrophin therapy for induction of ovulation and controlled ovarian hyperstimulation (COH) yielded 129 clinical pregnancies. Conventional IVF yielded 139 pregnancies. IVF and intracytoplasmic sperm injection (ICSI) with or without assisted hatching (AH) yielded 463 pregnancies, all during the same time period. The rates of multiple pregnancy (monozygotic and dizygotic) twins and triplets were recorded. MZT was found in 1.5% of ovulation induction or COH pregnancies (2/129). The incidence of MZT after conventional IVF was 0.72% (1/139). After IVF-ICSI/AH, MZT was found in 0.86% (4/463). The overall rate of MZT was 0.95% (7/731). Five cases were dizygotic triplets and two cases were monozygotic twins. We found the rate of MZT after assisted reproduction treatment increased more than two-fold over the background rate in the general population. Dizygotic triplets were found more often than monozygotic twins. The rate of MZT was consistently increased, irrespective of treatment modality or micromanipulation. This may signify that the aetiology of increased MZT after assisted reproduction is the gonadotrophin treatment rather than in-vitro conditions, micromanipulation, or multiple embryo transfer.     

Embryo reduction in multifetal pregnancies using saline injection: comparison between the transvaginal and the transabdominal approach.

A total of 30 patients with multifetal pregnancies, all resulting from treatment with superovulatory agents or assisted reproductive techniques, underwent embryo reduction. All patients had three or more fetuses (one sextuplet, two quintuplets, seven quadruplets and 20 triplets). The procedure was carried out using intra-embryonal injection of 0.9% sodium chloride solution. Embryo reduction was carried out via the transabdominal approach in 10 patients, performed at 11-12 weeks of gestation, and via the transvaginal route in 20 other patients, at 8-10 weeks of gestation. In the transabdominal group, one patient aborted following repeated attempts at embryo reduction while the other nine gave birth to healthy newborns (eight twins and one triplet). In the transvaginal group, four pregnancies are currently ongoing (all beyond 28 weeks of gestation), 14 pregnancies resulted in a delivery of at least one live newborn (13 twins and one singleton), one patient had a late abortion at 24 weeks' gestation and another was delivered at 27 weeks' gestation due to severe pre-eclampsia. Transvaginal ultrasound-guided needle procedures are commonly practised in most in-vitro fertilization units. The employment of this route for embryo reduction, performed at an earlier gestational age and with the use of a non-toxic substance such as 0.9% saline solution, is advocated.     

Obstetric outcome of 424 pregnancies after intracytoplasmic sperm injection

An evaluation of the outcome of pregnancies resulting from intracytoplasmicsperm injection for severe male factor infertility was conductedby analysing the data obtained from the patients and/or theirobstetrician/gynaecologist on standardized questionnaires. Thedata from 424 pregnancies between April 1991 and September 1994were analysed. Early pregnancy loss before 16 weeks occurredin 99 cases (23.3%), including 48 clinical abortions (11.3%),47subclinical pregnancies (11.1%) and four ectopic pregnancies(0.9%). Vanishing twins and triplets, which could be regardedas early embryonic wastage, were found in 36 cases (8.5%). Onepregnancy was interrupted at week 15 of gestation because ofanhydramnios, and four pregnancies (0.9%) ended in spontaneouslate abortions before 26 weeks. A total of 320 pregnancies (75.5%)resulted in the birth of at least one child; 222 of these (69.3%)were singletons, 93 were twins (29.1%) and five were triplets(1.6%). The problems of prematurity and low birthweight wereespecially related to the multiplicity of pregnancies. Furthermore,from among the total of 423 babies born, we have observed threecases of stillbirth and five cases of neonatal mortality. Theperinatal mortality rate was therefore 18.9 per 1000 births.The results of this study show that the obstetric outcome ofthese pregnancies was similar to that obtained after conventionalin-vitro fertilization and other assisted reproduction techniques.     

Maternal serum inhibin levels in twin and singleton pregnancies conceived by assisted reproduction

BACKGROUND: To investigate whether second trimester serum inhibin levels differ in pregnancies conceived by assisted reproduction technology (ART). METHODS: In Israel, serum samples from twin pregnancies were obtained for inhibin testing from women either referred for routine ultrasound monitoring, follow up after multi-fetal reduction or amniocentesis, largely for advanced maternal age. In the UK, inhibin had been tested prospectively in singleton and twin pregnancies of women having routine Down's syndrome (DS) screening. Results were available from 207 ART pregnancies: 170 singletons and 37 twins. This includes 15 twins from Israel, known to have been reduced from triplets to twins. Comparison was made with 4384 spontaneous pregnancies: 4334 singletons and 50 twins. Results were expressed in multiples of the gestation-specific median (MoM) for normal spontaneous pregnancies. RESULTS: In ART singletons, the median maternal inhibin level was higher (1.11 MoM) than in spontaneous singletons (0.99 MoM, P < 0.001, two-tail Wilcoxon Rank Sum Test). In twins, there was no material difference between ART and spontaneous pregnancies with medians of 1.98 and 2.18 MoM, respectively (P = 0.62). There was no effect of multi-fetal reduction, with medians of 1.76 and 1.81 MoM in reduced and non-reduced twins, respectively (P = 0.46). CONCLUSION: It appears that serum inhibin levels are increased on average in ART singletons but not in ART twin pregnancies. More data will be needed before deciding whether risk calculation parameters need to be altered when using inhibin for DS screening in pregnancy.     

Human chorionic gonadotrophin concentrations in early pregnancy after in-vitro fertilization.

There is increased risk of early pregnancy loss after assisted reproduction. In this study the use of serum human chorionic gonadotrophin (HCG) concentrations on day 12 after in-vitro fertilization (IVF) and embryo transfer was evaluated to predict pregnancy outcome. A total of 417 IVF pregnancies were included. Early pregnancy loss was defined as biochemical pregnancies, ectopic pregnancies and first trimester abortions. Vital pregnancies were defined as delivered singletons, multiple pregnancies and second trimester abortions. On the post embryo transfer day 12, the mean HCG concentration of the vital pregnancy group was significantly higher than in early pregnancy loss outcomes (P < 0.00001). Receiver operating characteristic (ROC) curve analysis was performed to evaluate the cut-off value of HCG giving maximal sensitivity and specificity in order to discriminate early pregnancy losses from vital pregnancies. A patient with a HCG value higher than the calculated cut-off value (55 IU/l) had a 90% chance of having a vital pregnancy after IVF and embryo transfer. It can be concluded that a discriminatory HCG value on day 12 after IVF and embryo transfer cycles may be useful in predicting pregnancy outcome and may guide clinicians in identifying those pregnancies at risk for adverse outcomes and instituting more intensive surveillance in this population.     

Perinatal outcome after in-vitro fertilization-surrogacy

The perinatal outcome of pregnancies (both single and multiple) established after in-vitro fertilization (IVF)-surrogacy was evaluated and compared to the outcome of pregnancies that resulted from standard IVF. Analysis of medical records and a telephone interview with physicians, IVF-surrogates, and commissioning mothers were conducted to assess prenatal follow up and delivery care in several hospitals. 95 IVF-surrogates delivered 128 liveborn (65 singletons, 27 sets of twins and two sets of triplets). The commissioning mothers and the IVF-surrogates average ages were 37.7 +/- 5.0 and 30.4 +/- 4.7 years old respectively. IVF-surrogates carrying twin and triplet gestations delivered substantially earlier than those who gestated singleton pregnancies (36.2 +/- 0.4 versus 35.5 versus 38.7 +/- 0.3 weeks gestation respectively; P < 0.001). Twin newborns were significantly lighter than singleton infants born through IVF-surrogacy (2.7 +/- 0.06 versus 3.5 +/- 0.07 kg; P < 0.001). The incidence of low birth weight infants rose from 3.3% in the single births to 29.6% (P < 0.01) in the twins and to 33.3% in the triplets born through IVF-surrogacy. The incidence of prematurity was significantly greater in both twins delivered by IVF-surrogates (20.4%) and infertile IVF patients (58%). The occurrence of pregnancy-induced hypertension and bleeding in the third trimester was four to five times lower in the IVF-surrogates, independently of whether they were carrying multiples. The incidence of Caesarean section was 21.3% for singleton gestations, while two times higher in the IVF-surrogates carrying multiples (56.3%). Postpartum complications occurred in 6.3% of patients and the incidence of malformation was similar to those reported for the general population. The results provide general reassurance regarding perinatal outcome to couples who wish to pursue IVF-surrogacy.     

Assistierte Reproduktionstechniken aus pädiatrischer Sicht

The number of multiple gestation births has increased due to assisted reproduction techniques. There is a higher risk of maternal and fetal complications in multifetal pregnancies compared with singletons. Twins have a five- to tenfold risk of preterm birth, which is even greater in higher multiple gestations. Increased morbidity and mortality are mainly caused by respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, and retinopathy, all of which are due to prematurity. Last but not least, one should not forget the emotional stress that parents of multiples are subjected to during pregnancy and after birth. Considering all these problems, multifetal pregnancies due to assisted reproduction techniques should be avoided, and the delivery of preterm twins should take place in a specialized perinatal unit.     

Obstetrical and neonatal outcome after controlled ovarian stimulation for IVF using the GnRH antagonist ganirelix

BACKGROUND: To establish long-term safety, follow-up data on pregnancy, birth and neonatal outcome were collected during clinical development trials with ganirelix (Orgalutran) in women undergoing controlled ovarian stimulation for conventional IVF or ICSI. METHODS: Results of an analysis of the pooled data of all follow-up data of the phase 2 and 3 programme for the development of ganirelix are presented. Obstetrical data on 340 ongoing pregnancies ( vertical line16 gestational weeks) after ganirelix treatment and 134 pregnancies after GnRH agonist treatment in a long protocol are shown. Furthermore, the neonatal outcome of 432 children [258 (75.9%) singletons, 72 (21.2%) twins and 10 (2.9%) triplets] born in the ganirelix group is presented and compared with 184 children [91 (67.9%) singletons, 36 (26.9%) twins and seven (5.2%) triplets] in the agonist group. RESULTS: There were no differences between the two groups in pregnancy loss after 16 weeks gestation. Incidence and nature of complications during pregnancy and delivery did not differ between the two groups. The overall mean gestational age was approximately 38.0 weeks, ranging from an average of 39 weeks for singletons to 34 weeks for triplets. No major differences were observed in neonatal characteristics of infants in the ganirelix and agonist groups, who had an overall mean birth weight of on average 3200 g for singletons, 2300 g for twins and 1800-1900 g for triplets. Congenital malformations were observed in 32 of 424 (7.5%) fetuses vertical line26 gestational weeks in the ganirelix group and in 10 of 181 (5.5%) in the agonist group. When applying a broad definition of major malformation (a major congenital malformation is a condition that causes functional impairment or requires surgical intervention) the rates were 4.5 versus 3.3 (odds ratio 1.37, 95% confidence interval 0.54-3.48) for the ganirelix and agonist group respectively. CONCLUSIONS: Reviewing the presented data and the literature on obstetric and neonatal outcome after conventional IVF or ICSI, we conclude that a controlled ovarian stimulation protocol including the novel GnRH antagonist ganirelix has been shown to be safe for pregnant women and their newborn babies.     

Maternal plasma concentrations of insulin-like growth factor binding protein-1 and placental protein 14 in multifetal pregnancies before and after fetal reduction

The aim of this study was to investigate the changes in maternalplasma insulin-like growth factor binding protein-1 (IGFBP-1)and placental protein 14 (PP14) in multifetal pregnancies beforeand after embryo reduction. Maternal plasma IGFBP-1 and PP14were measured serially in three groups of pregnant women at8–21 weeks gestation. Groups 1 and 2 were 12 singletonand 12 twin pregnancies achieved after in-vitro fertilization(IVF). Group 3 comprised 26 women with multifetal pregnanciesundergoing embryo reduction to twins. In the IVF pregnanciesmaternal plasma IGFBP-1 and PP14 increased with gestation toreach a peak at 20 and 10 weeks respectively; the mean concentrationsin twin pregnancies were significantly higher than in singletons.In multifetal pregnancies the mean plasma concentration of bothproteins was similar to that of IVF twin pregnancies beforereduction; after reduction, the values fell to less than thoseof twins. These findings suggest that the maximum secretorycapacity of the endometrium is achieved with twin pregnancies.In multifetal pregnancies undergoing iatrogenic reduction totwins, total residual endometrial function was less than intwin conceptions.     

Obstetric and perinatal outcome of children conceived from cryopreserved embryos

The main purpose of this study was to evaluate the obstetric and neonatal outcome of children conceived from cryopreserved embryos. The medical records of 270 infants (163 singletons, 98 twins and nine triplets) were reviewed and compared with two control populations of children born after in-vitro fertilization (IVF) with fresh embryos and children born after spontaneous pregnancies. The controls were matched according to maternal age, parity, plurality and date of delivery. In the cryopreserved group the gestational age at delivery for singletons was 279 +/- 13 days with birthweight 3476 +/- 616 g; for twins gestational age was 257 +/- 19 days with birthweight 2574 +/- 560 g; for triplets gestational age was 228 +/- 3 days with birthweight 1752 +/- 183 g. The incidence of preterm birth (< 37 weeks gestation) was 5.6% for singletons, 44.9% for twins and 100% for triplets. Seven children had major malformations (2.7%) and perinatal mortality occurred in two children (8/1000). Gestational age at delivery, birthweight, the incidence of malformations and the perinatal mortality were comparable with the two control groups both for singletons and twins. Significantly more singletons in the cryopreserved group were delivered by Caesarean section compared with the spontaneous group. The number of infants with low Apgar score (< 7 at 5 min) and the number of infants admitted to neonatal intensive care units were similar in the cryopreserved and spontaneous groups. In conclusion, the cryopreservation process did not seem to adversely influence fetal development and no increased perinatal risk was found.      

Elective single embryo transfer: the value of cryopreservation

In-vitro fertilization is associated with a high rate of multiple pregnancies, a consequence of the number of embryos transferred. There is a challenge in avoiding even twin pregnancies in assisted reproduction, and this can be accomplished with elective single embryo transfer and a good cryopreservation programme. In our follow-up study, we analysed all our elective single embryo transfers during 1998-1999. In all these cycles at least one embryo was frozen. A total of 127 elective single embryo transfers were performed with a clinical pregnancy rate of 38.6%. The highest implantation rate was obtained with four-cell embryos with <10% fragmentation (39.8%). Thirty-four patients have delivered (26.8%), one of these being a monozygotic pregnancy. In total 129 frozen-thawed cycles have been achieved in 83 patients. One frozen-thawed embryo has been transferred in 46 cycles with a clinical pregnancy rate of 17.4%, and two embryos have been transferred in 83 cycles, with a clinical pregnancy rate of 37.3%. Up until now, 66 of 125 patients in our single embryo transfer programme have delivered or have on-going pregnancies, and 77 still have embryos frozen. The cumulative delivery rate per oocyte retrieval is 52.8% and the twin rate 7.6%. We conclude that elective single embryo transfer with a good cryopreservation programme results in very acceptable pregnancy rates with a low risk of twins. This is a cost-effective practice that substantially reduces all risks associated with multiple pregnancies and lowers the cost per delivery.     

Maternal serum concentrations of pregnancy associated placental protein A and pregnancy specific {beta}-1-glycoprotein in multifetal pregnancies before and after fetal reduction

Placental function in multifetal pregnancies before and afterembryo reduction was investigated by measuring maternal serumconcentrations of pregnancy associated placental protein-A (PAPP-A)and pregnancy specific -1-glycoprotein (SP-1). Three groupsof pregnant women were studied following assisted reproduction;groups 1 and 2, were 12 singleton and 12 twin pregnancies respectively,and group 3 comprised 12 women with multifetal pregnancies undergoingembryo reduction. PAPP-A and SP-1 were measured serially at8–21 weeks gestation. In all pregnancies, maternal serumPAPP-A and SP-1 increased with gestation. In twin pregnanciesthe mean concentrations of SP-1 were significantly higher thanin singletons at all gestations, whereas for PAPP-A, concentrationswere similar between these groups. In multifetal pregnanciesbefore embryo reduction, the serum concentrations of both proteinswere significantly higher than in twin pregnancies. Followingreduction, the concentrations of PAPP-A remained significantlyhigher than for twins throughout, whereas the concentrationsof SP-1 gradually converged towards those of twins; by 19 weeksthere was no difference between the means of the two groups.These findings suggest that circulating concentrations of SP-1reflect total placenta mass, which is proportional to the numberof live fetuses, whereas the pattern of PAPP-A changes suggeststhat this protein is produced by the placenta, decidua and othertissues.     

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.      

Quintuplet pregnancy following transfer of two blastocysts: Case report

A 36-year-old single woman presented at the out-patient clinic in March 2000 requesting donor insemination. Between May 2000 and May 2001 she underwent six cycles of intrauterine insemination with donor sperm after clomiphene citrate stimulation without achieving a pregnancy. In January 2002, ICSI was performed; two embryos were transferred on day 3 and a dizygotic bichorionic pregnancy was achieved, which ended in a miscarriage at 21 weeks of gestation. After a second unsuccessful ICSI attempt in which a single embryo transfer was performed, she embarked upon her third attempt in March 2003 at 39 years of age. Two blastocysts were transferred after ICSI, resulting in a quintuplet gestation consisting of a monochorionic biamniotic pregnancy and a monochorionic triamniotic pregnancy. The current case report indicates that monozygotic pregnancies consisting of both twins and triplets are possible after treatment by assisted reproductive technologies. An association between extended culture, manipulation of the zona pellucida, ovarian stimulation and occurrence of monozygotic pregnancies has been suggested by retrospective studies. However, in order to identify more reliably predictive factors for the occurrence of monozygotic pregnancies, it is necessary to perform prospective trials.     

Babies born after ART treatment cost more than non-ART babies: a cost analysis of inpatient birth-admission costs of singleton and multiple gestation pregnancies

BACKGROUND: Currently, about one-third of infants born after assisted reproductive technology (ART) worldwide are twins or triplets. This study compared the inpatient birth-admission costs of singleton and multiple gestation ART deliveries to non-ART deliveries. METHODS: A cohort of 5005 mothers and 5886 infants conceived following ART treatment were compared to 245 249 mothers and 248 539 infants in the general population. Birth-admission costs were calculated using Australian Refined Diagnosis Related Groups and weighted national average costs (2003-2004 euro). RESULTS: ART infants were 4.4 times more likely to be low birthweight (LBW) compared with non-ART infants, translating into 89% higher birth-admission costs (euro2,832 and euro1,502, respectively). ART singletons were also more likely to be LBW compared with non-ART singletons, translating into 31% higher birth-admission costs (euro1,849 and euro1,415, respectively). After combining infant and maternal admission costs, the average cost of an ART singleton delivery was euro4,818 compared with euro13 890 for ART twins and euro54 294 for ART higher order multiples. Findings were not sensitive to changes in casemix. CONCLUSIONS: The poorer neonatal outcomes of ART singletons compared with non-ART singletons are significant enough to impact healthcare resource consumption. The high costs associated with ART multiple births add to the overwhelming clinical and economic evidence in support of single embryo transfer.     

Early transvaginal embryo aspiration: a safer method for selective reduction in high order multiple gestations.

Assisted reproduction technologies and ovulation induction for treatment of infertility continue to cause high order multiple gestations. Increased perinatal morbidity and mortality, as well as maternal morbidity, may complicate these pregnancies. Selective fetal reduction, an acceptable therapeutic approach in these cases, is usually performed at or after the ninth week of gestation, with KCl injected in the vicinity of the fetal heart, and is associated with a total pregnancy loss rate of 11.7%. We report our experience with 90 women who underwent early (mean 7.5 weeks gestation, range 7. 0-8.0 weeks) transvaginal selective embryo aspiration. The mean number of viable embryos before and after reduction was 3.5 and 2.1 respectively. Six (6.7%) pregnancies were lost before 24 gestational weeks. One miscarriage occurred at the tenth gestational week. The other five pregnancies were aborted at 17.3-21.6 weeks gestation. Additional interventions were performed in three of these pregnancies: genetic amniocentesis in two cases and cervical suture in one case. In the subset of 39 patients with>/=4 embryos, only one (2.6%) pregnancy loss was recorded. This loss rate is significantly lower (P < 0.05) than the 15.3% loss rate in patients with >/=4 fetuses calculated from other work. Four (4.4%) other pregnancies were complicated by premature delivery (25-28 weeks gestation). Mean gestational age of delivered pregnancies in our series was 35.7 weeks. In conclusion, early transvaginal embryo aspiration is a simple and relatively safe method for multiple pregnancy reduction. The overall pregnancy loss rate associated with early embryo aspiration is similar to that of procedures performed at later gestational age, but is significantly lower when the initial number of embryos is four or greater.     

Genetics: Genetic analysis prior to selective fetal reduction in multiple pregnancy: technical aspects and clinical outcome

Multiple pregnancies resulting from ovarian stimulation areat a higher risk of carrying at least one fetus affected byMendelian or chromosomal anomalies, the incidence of which isdirectly related to the order of multiples. Genetic analysisbefore fetal reduction was offered to both high-and low-riskpregnant women carrying two or more fetuses after ovulationinduction. Chorionic villus sampling (CVS) and fetal reductionwere achieved by transabdominal needling. The use of short-termculture, the polymerase chain reaction and fresh tissue enzymaticanalyses have made it possible for genetic diagnosis to be availablein a few days. A total of 100 patients had multifetal pregnancyreduction performed by a single operator; all of them completedpregnancy and none was lost at follow-up. The total fetal lossbefore 24 weeks was 7% and no statistically significant relationshipwas found with the final number of fetuses and CVS. Perinatallosses (3.9%) were only present in the series with a final numberof two fetuses. Pregnancy duration and birthweight were significantlyhigher in singletons than in twins, but were not related toCVS. The rate of chromosomal disorders was higher (7.2%) inthe study series than in singleton pregnancies not undergoingfetal reduction. Diagnostic error due to incorrect samplingwas reported in 1.5% of cases. These data support fetal reductionas a valuable strategy to improve the outcome of multiple pregnancy.The outcome of pregnancies reduced to singletons was significantlybetter than of those reduced to twins, and was not related toCVS. Therefore, prenatal genetic diagnosis should become anintegral part of counselling on multiple pregnancy, and is stronglyrecommended when reduction to singleton pregnancy is requested.     

Danish National In-Vitro Fertilization Registry 1994 and 1995: a controlled study of births, malformations and cytogenetic findings.

This paper reports data from the Danish in-vitro fertilization (IVF) registry from 1994 to 1995 including data on treatments and the results of these (perinatal outcome, cytogenetic findings and fetal malformations) in comparison with a control group matched for maternal age, parity, multiplicity and year of birth. There were 1756 deliveries of 2245 children (24.3% twins, 1.8% triplets). The rate of prematurity among IVF children was 23.8% (NS) [singletons 7. 3% (P < 0.05), twins 41.2% and triplets 93.5%], 23.6% weighed <2500 g [singletons 7% (P < 0.05), twins 42.2% and triplets 87.1%]. The perinatal mortality rate was 21.8 in the study group compared to 17. 4 in the control group (NS). In total, 13.2% of all clinical pregnancies and 15.4% of the pregnancies that resulted in a delivery had a prenatal genetic examination. Of all examined, 3.5% had an abnormal karyotype. In total, 107 (4.8%) children in the study group and 103 (4.6%) in the control group were born with malformations (NS), compared to 2.8% in the background population. Our results indicate that it is the characteristics of the patients and multiplicity of pregnancy, rather than the assisted reproductive technology that determines the fetal risks of IVF pregnancies compared to the background population.