Preterm delivery and growth restriction in multifetal pregnancies reduced to twins

Gestation at delivery, birthweight and pregnancy outcome of surviving fetuses from 127 multifetal pregnancies undergoing embryo reduction to twins were compared to 354 chromosomally normal non-reduced dichorionic twin pregnancies. First-trimester embryo reduction was carried out by intracardiac injection of KCl. In 16 (12.6%) of the 127 multifetal pregnancies reduced to twins, there was miscarriage of both fetuses before 24 weeks of gestation. The median interval between reduction and fetal loss was 5 weeks (range 1-12). In livebirths, the median gestation at delivery was 36 weeks (range 24-41) and the median difference in birthweight from the appropriate mean was -0.94 SD (range -3.89-1.73 SD). Both fetal loss before 24 weeks and the interval between embryo reduction and delivery were significantly associated with the gestation at reduction (r = 0.40, P < 0.001 and r = -0.57, P < 0.001 respectively). In the pregnancies reduced to twins compared to the non-reduced twins, the percentage of miscarriages was higher (12.6 compared to 2.5%; chi 2 = 19.2, P < 0.001), the median gestation at delivery was lower (36 compared to 37 weeks; t = -1.74, P < 0.05), and the median birthweight deficit was greater (-0.94 compared to -0.65 SD: t = -4.1, P < 0.001).      

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.     

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.     

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.     

Reduction of multifetal pregnancies to twins does not increase obstetric or perinatal risks.

Selective reduction in cases of multiple fetuses is used more often nowadays due to the increased number of multiple pregnancies resulting from assisted reproduction. In this retrospective study, we investigated whether twin pregnancies derived from fetal reduction carry a higher obstetric and perinatal risk compared to standard twin pregnancies. We found that the rate of miscarriage was 10.6% in the reduction group (n = 158) compared to 9.5% in the controls (n = 135). Mean gestational age at delivery was 35.7 weeks in the reduction group versus 35.1 weeks in the control group. Mean neonatal weight at birth was 2.260 g (800-3.750 g) in the reduction group compared to 2.240 g (540-3.360 g) in controls. Perinatal mortality rate was 49.3 per thousand after reduction and 42.0 per thousand in the control group. There was no statistically significant difference in any of the above parameters. Therefore, multifetal pregnancy reduction to twins does not appear to increase obstetric or perinatal risks.     

Obstetric outcome and psychological follow-up of pregnancies after embryo reduction.

The obstetric outcome and psychological follow-up of the parents after embryo reduction performed at Sahlgrenska University Hospital between 1993 and 1997 in 13 women treated for infertility is described. A comparison is made with non-reduced multiple pregnancies, both spontaneous and multiple pregnancies after assisted reproduction technology. Altogether 10 triplets, two quadruplets and one quintuplet pregnancy underwent embryo reduction. The surgical procedure was performed in gestation week 7-8 by transvaginal, ultrasound-guided aspiration of embryonic tissue. The psychological follow-up included personal interviews and psychological evaluations by a Psychological General Well-being Scale (PGWB) and Beck's Depression Inventory (BDI). In 11 cases reduction was performed to twin pregnancies. In two cases of triplets after in-vitro fertilization and transfer of two embryos, reduction was performed on the monozygotic, monochorionic twins. No complete miscarriages occurred. Ten women delivered twins and three women delivered singletons. The mean gestation length was 40.4 weeks for singletons and 35.9 weeks for twins. The mean birthweight was 3411 g for singletons and 2392 g for twins. No complications related to the reduction were detected in the children.The psychological follow-up showed that the psychological well-being of the parents was good. However, the events around the reduction were experienced as chaotic and emotionally disturbing. One woman regretted the reduction. All couples emphasized that avoidance of high order pregnancies should be of primary importance. In conclusion, embryo reduction appears to improve the perinatal outcome of multiple pregnancies obtained after assisted reproduction technology. It is important that the surgical procedure is performed at a centre with experience of this type of intervention, by a limited number of surgeons and in a regulated manner. Psychologically, however, the intervention is traumatic and psychological management is essential for good final outcome.     

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.     

Consequences of vanishing twins in IVF/ICSI pregnancies

BACKGROUND: Spontaneous reductions are a possible cause of the increased morbidity in IVF singletons. The aim of this study was to assess incidence rates of spontaneous reductions in IVF/ICSI twin pregnancies and to compare short- and long-term morbidity in survivors of a vanishing co-twin with singletons and born twins. METHODS: We identified 642 survivors of a vanishing co-twin, 5237 singletons from single gestations and 3678 twins from twin gestations. All children originated from pregnancies detected by transvaginal sonography in gestational week 8. By cross-linkage with the national registries the main endpoints were prematurity, birth weight, neurological sequelae and mortality. RESULTS: Of all IVF singletons born, 10.4% originated from a twin gestation in early pregnancy. Multiple logistic regression analyses adjusted for maternal age, parity and ICSI treatment showed for birth weight <2500 g an odds ratio (OR) of 1.7 [95% confidence interval (CI) 1.2-2.2] and for birth weight <1500 g OR 2.1 (95% CI 1.3-3.6) in singleton survivors of a vanishing twin versus singletons from single gestations; corresponding figures were seen for preterm birth. This increased risk was almost entirely due to reductions that occurred at >8 weeks gestation. We found no excess risk of neurological sequelae in survivors of a vanishing co-twin versus the singleton cohort; however, OR of cerebral palsy was 1.9 (95% CI 0.7-5.2). Furthermore, we observed a correlation between onset of spontaneous reduction, i.e. the later in pregnancy the higher the risk of neurological sequelae (r = -0.09; P = 0.02). Adjusted OR of child death within the follow-up period was 3.6 (95% CI 1.7-7.6) in the survivor versus the singleton cohort. CONCLUSIONS: One in 10 IVF singletons originates from a twin gestation. Spontaneous reductions that occur at >8 weeks gestation are one of the causes for the higher risk of adverse obstetric outcome in IVF singletons.     

Obstetric and neonatal outcome after single embryo transfer

BACKGROUND: Single embryo transfer (SET) pregnancies practically lack vanishing twins and may be associated with improved neonatal outcome. Our objective was to compare the obstetric and neonatal outcome of SET singletons with the outcome of singletons following double embryo transfer (DET) and spontaneous conception. METHODS: A 7-year (1997-2003) cohort of fresh SET (n = 269) and DET (n = 230, including 25 vanishing twins) cycles resulting in singleton birth at Helsinki University Central Hospital, Finland, was linked to the Finnish Medical Birth Register and the obstetric and neonatal outcome data compared with that from 15 037 spontaneously conceived singleton pregnancies. RESULTS: The obstetric and neonatal outcome of the SET group was comparable to that in the DET group. Compared with the comparison cohort, gestational hypertension (P = 0.005), placenta praevia (P < 0.001), preterm contractions (P = 0.01) and maternal hospitalization (P < 0.001) was more typical of women in the SET group. After adjusting for age, parity and socio-economic status the SET pregnancies showed increased risks of Caesarean section [odds ratio (OR) 1.54 with 95% confidence interval (CI) 1.18-2.00], preterm birth (OR 2.85; 95% CI 1.96-4.16) and low birthweight (OR 2.01; 95% CI 1.19-3.99) compared with the comparison cohort. CONCLUSIONS: Our results indicate that subject- and infertility-related mechanisms other than the number of transferred embryos influence the neonatal outcome of singleton IVF pregnancies.     

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.     

Attitudes of German infertile couples towards multiple births and elective embryo transfer

BACKGROUND: In Germany, embryo screening programmes combined with elective embryo transfer are illegal, but there is controversial debate about their legalization. Studies about the attitudes of infertile couples towards multiples, elective embryo transfer and multifetal reduction may help to illuminate how this law shapes patient choices. METHODS: A survey of 265 German infertile couples was conducted. Different logistic regression analyses were performed to assess independent factors associated with the parity for multiple births, approval for elective embryo transfer and multifetal reduction. RESULTS: Despite prior information about the risk of multiple births, 81% of respondents saw no risk in twin pregnancies and a sizable minority saw no risk even in triplet pregnancies. Eighty-nine percent of the respondents rated a twin pregnancy as desirable, whereas 35% rated a triplet birth as desirable. When presented with a choice of having multiple births versus having no biological children, 99% of the respondents endorsed twins, 84% triplets and 58% quadruplets. Seventy-four percent of the respondents approve of legalizing embryo screening programmes to select a good-quality embryo combined with elective embryo transfer. Ninety-two percent of the respondents rejected fetal reduction of twins. CONCLUSIONS: German infertile couples might conceivably be more willing to accept elective embryo transfer if screening for viable embryos was permitted.     

The feto-placental unit stimulates the pregnancy-associated increase in maternal bone metabolism

The aim of the study was to investigate role of the feto-placental unit in the pregnancy-induced increase in maternal bone metabolism. To achieve this, circulating concentrations of carboxy terminal pro-peptide of type I pro-collagen (PICP, a marker of bone formation) and cross-linked carboxy terminal telopeptide of type I collagen (ICTP, a marker of bone resorption) were measured in three groups of pregnant women. Group 1 comprised 12 women with singleton pregnancies; group 2, nine women with twin pregnancies; and group 3, 19 women with multifetal pregnancies (> or =3 fetuses) before and after selective fetal reduction to twin pregnancies. Blood samples were obtained at 10-12 weeks gestation (groups 1-3, pre-fetal reduction in group 3) and 4 weeks and 8 weeks later (groups 2 and 3). Before fetal reduction there was a significant correlation between the number of fetuses and the concentrations of both PICP and ICTP (r = 0.503 and P = 0.001 and r = 0.573 and P < 0.001 respectively). The circulating concentrations of PICP and ICTP were significantly higher in the pre-reduction multifetal pregnancies than in the twin pregnancies (P < 0.001 and P = 0.0013 respectively). The circulating concentrations of ICTP in multifetal pregnancies fell by 4 weeks after fetal reduction to those observed in control twins. Concentrations of PICP were unaltered after fetal reduction. Higher order multiple pregnancies had the greatest decline in ICTP concentrations. These data suggest that the increased bone turnover observed in the multifetal pregnancies is due to a factor derived from the feto-placental unit and that this factor acts primarily to stimulate bone resorption.     

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.     

Risks of miscarriage and early preterm birth in trichorionic triplet pregnancies with embryo reduction versus expectant management: new data and systematic review

BACKGROUND: Triplet pregnancies are associated with a high risk of miscarriage and early preterm birth. It is uncertain if the outcome is improved by embryo reduction (ER). METHODS: We examined trichorionic triplet pregnancies with three live fetuses at 10-14 weeks of gestation that were managed expectantly or by ER. The two groups were compared for the rates of miscarriage, defined as pregnancy loss before 24 weeks, and preterm delivery prior to 32 weeks. In addition, systematic searches were performed to identify studies comparing outcomes in expectant management versus ER in triplet pregnancies. RESULTS: We combined data from 365 pregnancies managed in our centre with those of five previous studies. In total there were 893 pregnancies. In the ER group (n=482) compared to the expectantly managed group (n=411), the rate of miscarriage was higher [8.1 versus 4.4%; relative risk (RR)=1.83, 95% confidence interval (CI)=1.08-3.16, P=0.036] and the rate of early preterm delivery was lower (10.4 versus 26.7%, RR=0.37, 95% CI=0.27-0.51, P<0.0001). It was calculated that seven (95% CI=5-9) reductions needed to be performed to prevent one early preterm delivery, while the number of reductions that would cause one miscarriage was 26 (95% CI=14-193). CONCLUSIONS: In trichorionic triplets, ER to twins is associated with an increase in the risk of subsequent miscarriage and decrease in risk of early preterm birth.     

The Brussels' experience of more than 5 years of clinical preimplantation genetic diagnosis

This paper describes the 5 years' experience of preimplantation genetic diagnosis (PGD) at the Brussels Free University. Our first PGD was carried out in February 1993. Up to October 1998, we carried out 183 PGD cycles on fresh cleavage embryos of 92 couples for 25 different conditions. Patients were treated for autosomal recessive (n = 39), autosomal dominant (n = 65) and X-linked recessive (n = 47) monogenic disorders as well as for autosomal structural aberrations (n = 10), sex chromosome numerical and structural aberrations (n = 21) and a combination of the two latter (n = 1). Specific diagnosis was carried out by polymerase chain reaction (n = 108). Fluorescence in-situ hybridization was used for sexing (n = 64) and structural aberrations (n = 11). We transferred 1.6 +/- 1.1 embryos per cycle, resulting in an implantation rate of 12.0% per replaced embryo. Ongoing pregnancies were achieved in 29 cycles, i.e. 23 singletons, five twins and one dichorionic triplet with an acardius acranius. The ongoing pregnancy rates per cycle, per transfer and per couple were 16.4, 19.9 and 31.5% respectively. While 28 ongoing pregnancies resulted in the births of 34 infants, one pregnancy was terminated after misdiagnosis. The results of 24 PGD were confirmed by prenatal diagnosis or after birth while no information was available in four pregnancies. Our series demonstrates that PGD is a feasible technique by which to avoid the birth of genetically affected children to couples at risk.     

A 3 year, prospectively-designed study of late selective multifetal pregnancy reduction

The aim of our study was to evaluate the pregnancy outcomes of late selective multifetal reduction (MFPR). We performed a 3 year, prospectively-designed study in which 28 patients underwent MFPR at a mean gestational age of 20.2 +/- 3.9 weeks (range 14-29 weeks). The indications for MFPR included: multiple gestation (> or = 3) (57%), structural anomaly (29%), and chromosomal abnormality (14%). The procedure was performed using ultrasonographically-guided intracardiac injection of potassium chloride. The mean gestational age at delivery was 36.6 +/- 2.2 weeks (range 31-40 weeks). Nine patients (32%) delivered before 36 weeks of gestation. The mean birth weight was 2370 +/- 614 g (range 1510-3250 g). Discordancy was evident in four twins (14%), and intrauterine growth retardation in four pregnancies. One case (3.5%) presented with oligohydramnios, and one with pregnancy- induced hypertension. One case of late abortion due to passive cervical dilatation 4 weeks after the MFPR was observed. Procedure-related amnionitis followed by late abortion occurred in one case. A total of 57% of the patients delivered vaginally and 43% delivered by Caesarean section. We concluded that late selective MFPR is associated with favourable perinatal outcome. Late MFPR may facilitate the detection of structural and chromosomal anomalies prior to the procedure, and the accomplishment of selective reduction of the affected fetus.      

The obstetrical and neonatal outcome of babies born after single-embryo transfer in IVF/ICSI compares favourably to spontaneously conceived babies

BACKGROUND: Recently, concern has risen about poor obstetrical and neonatal outcome of singletons after IVF/ICSI. Because the population of patients receiving single-embryo transfer (SET) resulting in singleton pregnancies is different from the one that would have become pregnant (with a singleton) before SET was introduced, we wanted to investigate whether the outcome of singleton pregnancies after SET differed from spontaneously conceived singletons. METHODS: The obstetrical and early neonatal outcome of all pregnancies originating from SET after IVF/ICSI procedures between 1 January 1998 and 31 December 2003, was prospectively collected and analyzed. RESULTS: Data from 251 singleton pregnancies and births after SET were analyzed and compared to data from 59,535 spontaneously conceived singletons retrieved from the Centre for Perinatal Epidemiology. The mean birthweight of the singletons after SET was 3322 g (+/-538 SD) versus 3330 g (+/-531 SD) for the spontaneously conceived singletons (P = 0.82). The mean gestational age was 38.7 weeks (+/-1.9 SD) for SET and 38.9 weeks (+/-1.8 SD) for spontaneously conceived singletons (P = 0.06). The proportion of very preterm birth (<32 weeks) was 0.8% in each group, and the proportion of preterm birth (<37 weeks) was 10.0% for SET singletons and 6.24% for spontaneous singletons (P = 0.03). However, mean birthweight of very preterm, preterm and term SET singleton babies was similar to the mean birthweight in every category of gestational age in the spontaneous conceived control group. Stillbirth was 0.4% for both populations (P = 0.99). CONCLUSIONS: Good prognosis patients, in whom SET is applied, do not only have a higher chance of conception but do not have an unfavourable outcome of their singleton baby when compared to spontaneous singletons.     

Pregnancy outcome and neonatal data of children born after ICSI using testicular sperm in obstructive and non-obstructive azoospermia

BACKGROUND: Registries on outcome of ICSI pregnancies obtained with testicular sperm do not differentiate between obstructive (OA) and non-obstructive azoospermia (NOA). We evaluated the pregnancy outcome and neonatal data on children born after ICSI using testicular sperm of men with histologically proven OA or NOA. METHODS: Pregnancies obtained after ICSI using testicular sperm of men with defined NOA (n = 70) were compared with those of men with OA (n = 204). RESULTS: Multiple birth rates in NOA and OA couples, respectively, were 21 versus 27% (P = NS), overall preterm delivery rates were 38 versus 26% (NS), and prematurity rates were 24 versus 13% for singletons (NS) and 86 versus 54% for twins (relative risk 1.59, 95% confidence interval 1.04-2.42). Median gestational age for singletons was 38.3 versus 39.3 weeks, respectively (P < 0.05). The low birth weight rates were 34 versus 31%, respectively (NS). The early perinatal mortality rate was 66 versus 15 per 1000 births, respectively, (NS). Major congenital malformations were observed in 4 versus 3%, respectively, of the live born babies (NS). Prenatal karyotypes showed 7% de-novo abnormalities in the NOA group versus 1% in the OA group (NS). CONCLUSIONS: Our data do not show differences between NOA and OA pregnancies except for a strong tendency towards a lower gestational age in singletons and a higher percentage of premature twins in the NOA group. Although our data are based on a limited sample, the differences observed call for further analysis. Given the low pregnancy rates after ICSI with NOA, a multicentre study, differentiating NOA and OA patients, would be recommended.     

Is intracytoplasmic sperm injection (ICSI) a safe procedure? What do we learn from early pregnancy data about ICSI?

The aim of this study was to evaluate the safety of the intracytoplasmicsperm injection (ICSI) procedure by analysing early pregnancydata from ICSI and in-vitro fertilization (IVF) patients. Inall, 50 ICSI pregnancies were compared with 226 FVF pregnancies.Comparisons were made during the first 9 weeks after the theoreticallast menstrual period (7 weeks after oocyte retrieval) withregard to epidemiological data, plasma hormonal concentrationsand transvaginal ultrasonographical findings. Although patientswere significantly (P < 0.001) younger in ICSI (31 years)than in IVF pregnancies (33 years), their duration of infertilitywas similar. Miscarriage and multiple gestation rates were notsignificantly different in ICSI pregnancies (respectively 24and 24%) from those found after IVF (32 and 29%). The probabilityof developmental arrest of the intrauterine sac (miscarriagesand vanishing twins) was similar in both ICSI (16%) and IVF(25%) cases. The mean plasma hormonal concentrations startingfrom day 11 after oocyte retrieval were similar in both groups.Every ICSI and IVF pregnancy showed an embryo with cardiac activityat 7 weeks. Early pregnancy data did not show any abnormal findingsfor pregnancies achieved using ICSI compared to those achievedby FVF.     

Characterization of a top quality embryo, a step towards single-embryo transfer.

In most in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) programmes approximately one ongoing pregnancy in three is multiple. The need to characterize embryos with optimal implantation potential is obvious. We retrospectively examined all of 23 double transfers resulting in ongoing twins, occurring between January 1, 1996 and May 19, 1997. Characteristics of these top quality embryos were absence of multinucleated blastomeres, four or five blastomeres on day 2, seven or more cells on day 3, and 2 embryos, 11/31 (35%) were multiple. We applied our top quality criteria to the 221 double transfers: 106 transfers with two top embryos resulted in 65 (63%) ongoing pregnancies with 37 (57%) twins, 65 transfers with one top embryo in 38 (58%) ongoing pregnancies with eight (21%) twins. In the group without top embryos, 12/52 (23%) ongoing singletons occurred, with no twins. The corresponding ongoing implantation rates were 49, 35 and 12%. This analysis suggests that single embryo transfer with an acceptable pregnancy rate might be considered if a top quality embryo is available.