Multiple Pregnancy Outcomes Research Articles

The Effect of a Comprehensive Incentive Program on Patient Participation in Elective Single Blastocyst Transfers

Most IVF programs are able to limit higher order multiple pregnancies. In this program, twin pregnancy rates of more than 50% are common when two blastocysts are transferred (Meintjes et al; 2004). The pandemic of twin pregnancies can only be curtailed further by the routine transfer of a single blastocyst. The objective of this study was to increase patient participation in elective single blastocyst transfer (SBT) with the help of a comprehensive educational and monetary incentive program without compromising clinical pregnancy outcomes. Elective single blastocysts for transfer were initially offered to good prognosis patients based on transfer-day embryo quality without any additional incentive and limited education. A formal facility and physician incentive plan was then adopted in an effort to increase voluntary patient participation. Endpoints measured included patient acceptance rate, ongoing and multiple pregnancy outcomes as summarized in the table. Single blastocyst transfer was initially offered to patients ≤37 years of age and to patients using donor oocytes with at least two freeze quality blastocysts available at the time of transfer. After introduction of the formal incentive program, patients were asked to sign an agreement to elect or refuse a single blastocyst for transfer. Patients were educated on the risks and potential serious consequences associated with twin pregnancies, the availability of a SBT incentive and the need to make a decision on the day of blastocyst transfer. As part of the incentive, free cryopreservation and limited storage of blastocysts was offered when transferring a single blastocyst regardless of pregnancy outcome. Should the SBT not result in a live birth, the facility and physicians agreed to perform a subsequent frozen-thawed blastocyst transfer cycle at no additional cost. The twin rate for patients with SBT was 2.7%. In contrast, the twin rate for patients declining a SBT was 78.8%. In addition, one triplet pregnancy occurred in the patient group declining SBT. All patients who elected a SBT had embryos cryopreserved. The cumulative fresh/frozen ongoing and term pregnancy rates for SBT was 74.6%. Similiarly, the cumulative fresh/frozen ongoing and term pregnancy rates for patients who declined SBT and transferred two embryos was 79.9%. Tabled 1 Even though SBT was offered to selected patients, the average number of embryos transferred to all donor recipients and day five transfers were reduced to less than two. Participation in SBT more than doubled for patients using donor oocytes and almost doubled for patients using their own oocytes after the incentive plan was formally introduced. Cumulative ongoing and term pregnancy rates were not affected when transferring single blastocysts within donor oocyte and patient groups. Finally, this study proves that when providing a significant incentive, two out of three patients will choose a SBT when properly educated without any cohersion.

Multifetal pregnancy reduction in pregnancies with a monochorionic component

We conducted a retrospective, cross-sectional study to evaluate the efficacy, safety, and effect of first-trimester multifetal pregnancy reduction on procedure-related complications and obstetrical outcome in multiple pregnancies with a monochorionic component. Although procedure-related complications were relatively common, the obstetrical outcome was favorable in most cases when the monochorionic twin component was reduced.

First-trimester fetal reduction to a singleton infant or twins: Outcome in relation to the final number and karyotyping before reduction by transabdominal chorionic villus sampling

The purpose of this study was to evaluate fetal outcome and maternal complications of multifetal pregnancy reduction to a single fetus or twins. To evaluate safety and efficacy of transabdominal chorionic villus sampling for karyotyping before fetal reduction. Four hundred twenty-four consecutive multiple pregnancies were reduced to twins (255 pregnancies) or a single fetus (169 pregnancies) at 8 to 13 weeks of gestation after transabdominal chorionic villus sampling for fetal karyotyping. Fetal and maternal outcome were observed prospectively and compared with control series of twin (147) and singleton (885) pregnancies in which reduction procedures were not performed. Transabdominal chorionic villus sampling was performed successfully in 100% of the cases. The accuracy of karyotyping was 99.2%. The overall pregnancy loss rate after reduction was 3.3%. No differences were observed between study and control series for severe prematurity, low birth weight, and neonatal deaths. Mean gestational age at delivery (35.2% vs 38.1%) and mean birth weight (2180 g vs 2873 g) were significantly lower; preterm delivery (64% vs 11%), neonatal death (3.4% vs 0.6%), and maternal complications (42.8% vs 9.5%) were significantly higher when the reduction was to twins rather than in reduction to a single fetus. Pregnancy loss rate did not differ between study series. The overall rate of chromosomal abnormalities in the study series was higher (relative risk, 2.0) than in singleton control series. The outcome of multiple pregnancies that were reduced to a single fetus or twins was similar to that of nonreduced pregnancies; fetal and maternal complications were significantly lower in the series of pregnancies that were reduced to a single fetus. The safety and efficacy of transabdominal chorionic villus sampling and the higher pregnancy rate of chromosomal abnormalities in multiple pregnancies imply that fetal karyotyping should be advised before fetal reduction.

Spontaneous embryonic loss after in vitro fertilization with and without intracytoplasmic sperm injection

To determine whether pregnancies after IVF, with and without intracytoplasmic sperm injection (ICSI), have different early spontaneous loss rates. Retrospective analysis of IVF/ICSI dataset. The Center of Reproductive Medicine, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy. Women undergoing IVF with or without ICSI. First-trimester sonography at 6-7 weeks to count the number of embryos with positive heartbeat. The number of embryos lost was calculated from a second-trimester sonogram. Embryonic loss rates related to the initial number of embryos, maternal age <35 or > or =35 years, and IVF procedure. In vitro fertilization and ICSI had similar embryonic loss rates (odds ratio [OR] 1.2, 95% confidence interval [CI] 0.9-1.7, and OR 1.3, 95% CI 0.9-1.8 for women aged <35 years and > or =35 years, respectively). Younger women had fewer losses after IVF (OR 0.7, 95% CI 0.5-0.9). Multiples had lower loss rates compared with singleton pregnancies. In vitro fertilization and ICSI have similar spontaneous embryonic loss rates. Factors other than the initial number of embryos, maternal age, and IVF technique, such as embryo quality or uterine environment, might be involved in the outcome of multiple pregnancies in assisted reproductive technology procedures.

P12.16: Risk factors and outcome of multiple pregnancy

P12.16: Risk factors and outcome of multiple pregnancy

Improving multiple pregnancy outcomes with nutritional interventions.

Improving multiple pregnancy outcomes with nutritional interventions.

Aneuploidy screening of preimplantation embryos using comparative genomic hybridization versus fluorescence in situ hybridization techniques

When the results of comparative genomic hybridization (CGH) technology are compared with aneuploidy screening panels routinely run on fixed blastomeres using fluorescence in situ hybridization (FISH), it appears that CGH could act as an additional tool to determine which of a set of preimplantation embryos have a balanced karyotype. This information could lead to lower numbers of embryos transferred, potentially lowering multiple pregnancy outcomes. The CGH and FISH analyses can also be useful in explaining why some patients do not conceive after multiple embryo transfer attempts, which have added up to a total of two dozen or more embryos transferred to a single patient over successive transfers.

The role of patient age when deciding to transfer at the blastocyst stage. should we be more aggressive with day 3 transfers in older patients?

Objective: It is suggested by some that blastocyst transfers should be performed for all patients, regardless of age and embryo quality. However, the majority of blastocyst programs maintains that pregnancy outcomes can be optimized by the “rescue” transfer of some embryos at earlier stages of development. The objectives of this study were to evaluate if clinical- or multiple pregnancy outcomes are compromised under the following circumstances and, if so, if it could be related to age. The two circumstances would be when 1) embryos are transferred at the cleavage stage when supernumary embryos are available for selection or when 2) embryos are cultured to the blastocyst stage for transfer when limited numbers of quality embryos are available at the cleavage stages.

Using 100% embryo implantation IVF cycles to identify preferred embryo development patterns—morphokinetics

Objective: Eliminating multiple gestations from assisted reproduction requires performing single embryo transfers (ET). This rests on the pre-transfer selection of a single, developmentally competent embryo from the cohort of available embryos. Primary methods for assessing embryo competence have not clarified the dynamic relationship between patterns of embryo development (morphokinetics) and the odds of implantation. We used cycles resulting in 100% embryo implantation to identify preferred morphokinetic patterns that predict favorable IVF-ET outcomes. Design: University based retrospective cohort study conducted from 1/01/02–11/30/02. Materials and Methods: Individual embryo culture allowed daily evaluation of embryos. Morphokinetic patterns were assigned based upon blastomere number and cell symmetry observed at 48 and 72 hours post retrieval. 100% embryo implantation was defined by sonographic confirmation that embryonic sac number equaled the number of embryos returned. The most common (Preferred) morphokinetic patterns resulting in 100% implantation were used to screen all fresh, non-donor ET cycles performed during the study period and analyzed for an association with cycle outcome. Statistical analysis was carried out using χ2 with p < 0.05 considered statistically significant. Results: Forty-five cycles (96 embryos) resulted in 100% implantation. These 96 embryos displayed 36 morphokinetic patterns. 5 Preferred morphokinetic patterns described 53.1% of the implanted embryos (Table 1). Considering the ET cycles that did not display 100% implantation, cohorts containing at least 1 embryo with 1 of the 5 Preferred morphokinetic patterns had significantly higher pregnancy and implantation rates regardless of whether the embryo exhibiting this pattern was transferred (Table 2). Table 1Description of Preferred morphokinetic patternsTable 2IVF-ET outcome according to embryo disposition and embryo availability of Preferred morphokinetic patternTable 2IVF-ET outcome according to embryo disposition and embryo availability of Preferred morphokinetic patterna p < 0.002 when compared to all other groups. b p < 0.04 when compared to all other groups. a p < 0.002 when compared to all other groups. b p < 0.04 when compared to all other groups. Conclusion: By analyzing embryo morphokinetic patterns in 100% implantation cycles, we identified 5 Preferred embryo development patterns. Screening all ET cycles for Preferred patterns suggests that they can aid in prognostication. Non-invasive morphokinetic assessment provides the opportunity to identify developmentally competent embryos and thereby designate cycles for single ET. This may aid in maintaining IVF-ET pregnancy rates and curtail multiple pregnancy outcomes.

Human Chorionic Gonadotropin Levels are Predictive of Pregnancy Outcomes: 248 Blastocyst Transfers

Objective: To determine the predictive value of β-hCG serum levels at days 14 and 16 post-retrieval for pregnancy outcome following blastocyst transfer. Design: Cohort analysis of 248 blastocyst transfers in 248 patients at a university-based assisted reproductive science center from January 1998 to December 1999. Materials and Methods: 248 Blastocyst transfers were consecutively studied. β-hCG serum samples were analyzed at day 14 and day 16 after retrieval. Pregnancy outcomes were followed through 12 weeks of gestation. Differences were evaluated using the Student t-test and Fisher’s exact test where appropriate. A p value of <0.05 was considered significant. Results: A total of 248 patients received 522 blastocysts transfers for an overall clinical pregnancy rate per transfer of 64.5% and an implantation rate (IR) of 46.2% per transfer. The average number of blastocysts transferred was 2.01. Twenty-six (10.5%) of the 248 transfers ended in spontaneous abortions (SABs), and one in an ectopic pregnancy (0.4%). The mean age of patients with SABs was statistically higher than ongoing pregnancies (p<0.05). Of the clinical pregnancies (n=160) 40% were singletons, 39.4% were twins, and 3.75% were triplets. β-hCG serum levels of SABs were lower than ongoing pregnancies for day 14 and for day 16 (p<0.05) respectively. Also, there were significant differences in β-hCG serum levels on day 16 between twin and singleton gestations (p<0.05). The rate of change of β-hCG between d14 and d16 was also analyzed. We found that this rate of change was significantly different between twins and singletons (p<0.05) and between SAB’s and ongoing pregnancies (p<0.05). For Serum values >100 mIU/mL on day 14 and >250 mIU/mL on d16 the sensitivity was 94% to detect ongoing pregnancies. At day 14 the sensitivity to detect for multiple pregnancies for a β-hCG ≥200 was >80%. Tabled 1Pregnancy outcomeNo. of patientsAge (±SEM)Day 14 (±SEM)Day 16 (±SEM)SABs2634.4 ± 0.769.3 ± 10.4176.5 ± 26.3Singleton6433.0 ± 0.597.7 ± 7.5147.3 ± 32.2Twins6331.8 ± 0.4167.7 ± 11.8494.1 ± 41.1Ongoing13332.4 ± 0.3135.7 ± 7.9403.6 ± 28.8 Open table in a new tab Conclusion: This is the first report of β-hCG values and their ability to predict pregnancy outcomes following blastocyst transfer. Serum β-hCG levels at day 14 and day 16 following retrieval were strongly predictive for ongoing and multiple pregnancy outcomes in patients undergoing blastocyst transfer.

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 and perinatal outcomes of multiple pregnancy following IVF-ET

Objective: To analyze the course of pregnancy and perinatal outcome in 31 twins, 22 sets of triplets and five quadruplet clinical pregnancies following conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) procedures and in relation to 58 singleton pregnancy following the same procedure. Methods: Retrospective analysis of maternal and neonatal medical records of 58 singleton, 31 twin, 22 triplet and five quadruplet pregnancies diagnosed at 7–8 weeks gestation following 561 embryo transfer procedures in 628 oocyte collections at the IVF Center in the Maternity Hospital, Kuwait from July 1994 to December 1996. Results: The clinical pregnancy rate in 628 cycles proceeding to oocyte collection was 32.6%, there being 58 singletons (50.6%), 31 twins (33.5%), 22 triplets (10.8%) and five quadruplets (2.5%). Early complicated outcomes included 47 miscarriages (23.7%), four ectopic pregnancies (1.9%) and one hydatidiform mole. The spontaneous fetal reduction rate was 20.6% in twin, 45.5% in triplet and 40% in quadruplet pregnancies. There was a significantly higher maternal and neonatal complication rate in the triplet group compared to singletons and twins, including threatened miscarriage, pre-eclampsia, antepartum hemorrhage, longer hospital stay and preterm labor. The chance of operative delivery was higher in high-order multiple pregnancy (HOMP). The major neonatal complications were related to prematurity. Neonatal morbidity and mortality were significantly higher in the triplet group. The need for admission to the Special Care Baby Unit (SCBU) and the Neonatal Intensive Care Unit (NICU) was significantly higher in HOMP. However, there were no statistically significant differences in the perinatal mortality in relation to the degree of HOMP. Conclusion: Maternal complications, perinatal and neonatal morbidity after 2 years activities in the IVF Center have been reviewed leading to changes in policies of management, notably a reduction in the number of embryos transferred.

1 Adverse outcome after multiple pregnancy

There is increasing interest in the outcomes of multiple pregnancies as their numbers rise, mainly owing to advances in fertility-enhancing techniques. In addition, the numbers of multiple births surviving the perinatal period is increasing with the increasing survival of very tiny babies. In order to investigate these outcomes or to evaluate procedures that may improve them, it is important to consider a number of methodological issues that affect the comparability of data both between and within populations. How a birth and a multiple birth are defined, data sources, whether multiple pregnancies or individual births are being counted and the identification of multiple gestations by zygosity and chorionicity will all affect the reported outcome rates. In light of this, perinatal mortality and neurodevelopmental disabilities are examined as adverse outcomes of multiple pregnancies.

Multifetal pregnancy reduction: A review of the world results for the period 1993–1996

The objective of this work was to evaluate the outcome of multifetal pregnancy reduction and to provide an analysis of the ethical dilemmas associated with its application. The study design was based on data on over 1400 completed pregnancies that underwent multifetal pregnancy reduction as reported in the world literature during 1993–1996. The results were: A total of 1453 completed cases of multifetal pregnancy reduction are presented. The total survival rate was estimated to be 87.7%, resulting in a total pregnancy loss rate of 12.3%. The lowest survival rate is found to be in higher-order pregnancies of five or more fetuses (75.2%), whereas pregnancy loss rate seems to be similar for quadruplets, triplets and twins that underwent reduction (11.3%, 8.3% and 13.6%, respectively). A 33.3% of the total pregnancy loss rate occurred within four weeks from the procedure, whereas 66.7% occurred after the four weeks but at 24 weeks of gestation or earlier. The mean gestational age at delivery was estimated to be 33 weeks for pregnancies reduced to triplets, 35.8 weeks for those reduced to twins and 36.9 weeks for singletons, with 5% delivering at less than 28 weeks and 9.6% at 29–32 weeks. We conclude that multifetal pregnancy reduction has been established as an efficient and safe way to improve outcome of multifetal gestations, especially those with four or more fetuses and likely of triplets. As the experience from the procedure increases, it seems that reduction of triplets to twins can be offered to patients with satisfactory results. The reduction to singletons has not yet been established and is being performed only when medical indications exist. Prenatal genetic diagnosis should become an integral part of counselling on multiple pregnancy. Physicians should take whenever possible measures designed to prevent high multiple birth pregnancies. We also note that although multifetal pregnancy reduction improves significantly the outcome of multiple pregnancies, several ethical dilemmas arising from its application are still under dispute.

Multiple pregnancy outcome at age 35 and older

Multiple pregnancy outcome at age 35 and older

The outcome of multiple pregnancy.

The incidence of multiple pregnancy and delivery has increased dramatically over the past 10-15 years in many developed countries of the world. Data for England and Wales show that between 1980 and 1993 the twin maternity rate increased by approximately 25% and the triplet and higher order maternity rate more than doubled. Similar trends have been reported elsewhere. The majority of these increases have been linked to the use of ovarian stimulants and assisted reproduction techniques, and multiple pregnancy must be considered to be one of the most important adverse outcomes in current methods of infertility treatment. Obstetric complications associated with multiple pregnancy include prenatal screening problems and increased incidence of pregnancy-induced hypertension, antepartum haemorrhage, preterm labour and assisted or surgical delivery. Neonatal problems include low birthweight and increased prevalence of congenital malformations. Compared with singletons, neonatal mortality was seven times higher in twins and > 20 times higher in triplets and higher order births in England and Wales in 1991. Survivors also suffer higher rates of cerebral palsy and other neurological impairments. Most studies of pregnancies and babies resulting from assisted reproduction have demonstrated similar, if not higher, risks of adverse obstetric and neonatal outcomes for multiple births compared with national expectations. A poorer outcome in multiple pregnancy, especially in triplet and higher order pregnancy, supports the replacement of two good quality embryos in assisted reproduction treatment cycles.

Outcomes of multiple pregnancies in female liver transplant recipients: [formula omitted] Dept. of Surgery, Thomas Jefferson University, Philadelphia, PA and ∗University of Arizona, Tucson, AZ

Outcomes of multiple pregnancies in female liver transplant recipients: [formula omitted] Dept. of Surgery, Thomas Jefferson University, Philadelphia, PA and ∗University of Arizona, Tucson, AZ

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

Multiple pregnancies resulting from ovarian stimulation are at a higher risk of carrying at least one fetus affected by Mendelian or chromosomal anomalies, the incidence of which is directly related to the order of multiples. Genetic analysis before fetal reduction was offered to both high- and low-risk pregnant women carrying two or more fetuses after ovulation induction. Chorionic villus sampling (CVS) and fetal reduction were achieved by transabdominal needling. The use of short-term culture, the polymerase chain reaction and fresh tissue enzymatic analyses have made it possible for genetic diagnosis to be available in a few days. A total of 100 patients had multifetal pregnancy reduction performed by a single operator; all of them completed pregnancy and none was lost at follow-up. The total fetal loss before 24 weeks was 7% and no statistically significant relationship was found with the final number of fetuses and CVS. Perinatal losses (3.9%) were only present in the series with a final number of two fetuses. Pregnancy duration and birthweight were significantly higher in singletons than in twins, but were not related to CVS. The rate of chromosomal disorders was higher (7.2%) in the study series than in singleton pregnancies not undergoing fetal reduction. Diagnostic error due to incorrect sampling was reported in 1.5% of cases. These data support fetal reduction as a valuable strategy to improve the outcome of multiple pregnancy. The outcome of pregnancies reduced to singletons was significantly better than of those reduced to twins, and was not related to CVS.(ABSTRACT TRUNCATED AT 250 WORDS)

Maternal-Fetal Transmission of HIV-1-Reply

In Reply. —Dr Sarkar points out that multivariate analysis of the potential factors associated with maternal-fetal transmission would be preferable to a univariate analysis. We agree. However, because of the small sample size of our cohort and the large number of variables, this was not possible and would have added nothing to our results. We hope that as our cohort size increases this will become possible. We analyzed all of the factors outlined in Table 2 of the original article stratified for zidovudine use. As discussed in the article, we found that the observations of increased transmission risk, associated both with exposure to maternal blood and with the presence of maternal p24 antigemia, were even more significant in the zidovudine-untreated mothers. The problem of dealing with the analysis of results based on infant outcome in multiple pregnancies and twins is difficult, but we based our assumptions on the fact that

First‐trimester prenatal diagnosis in quintuplets: A practical approach using step‐by‐step embryo reduction

A multiple pregnancy of high rank may occur in a couple at risk for a Mendelian disorder. Prenatal diagnosis is hampered by the difficulty of (1) obtaining chorionic villi from each zygote and (2) unequivocally relating each sample to the corresponding embryo. The calculation of the genetic risk according to the number of zygotes led us to propose a diagnostic strategy based on embryo reduction, a technique initially designed to improve the perinatal outcome of multiple pregnancies with normal embryos. We report a case in which this approach allowed rational use of first-trimester chorionic villus sampling in a quintuplet pregnancy at risk for non-ketotic hyperglycinaemia, resulting in the selective birth of unaffected twins.