Pregnancy outcome after multifetal pregnancy reduction to twins compared with spontaneously conceived twins

Multifetal pregnancy reduction (MFPR) appears to be an efficaciousmethod for improving the perinatal outcome of ‘high order’multifetal gestations. The present study was undertaken to evaluatepregnancy outcomes after MFPR to twins in comparison with spontaneouslyconceived twins. In all, 10 patients with quadruplet gestations(group 1) and 30 patients with triplet gestations (group 2),who underwent MFPR to twins, were prospectively enrolled. Pregnancycomplications, gestational age at delivery, mode of deliveryand birthweights were compared with 30 consecutive spon-taneoustwin gestations (group 3) matched by maternal age and parity.Mean gestational age at delivery and mean birthweights weresignificantly lower in group 1, compared with groups 2 and 3(33.2, 35.9, 36.9 weeks, and 1843, 2209, 2361 g respectively).The incidence of pregnancy complications was significantly higherin group 1 compared with group 3. There was also a clear trendof increased incidence of specific pregnancy complications ingroup 1 compared with groups 2 and 3, especially premature contractions(PMC; 50, 27 and 13% respectively), and pregnancy-induced hypertension(PIH; 40, 23 and 7% respectively). In conclusion, the initialnumber of fetuses before reduction was inversely correlatedwith gestational age at delivery and birthweight, and positivelycorrelated with pregnancy complications. Contrary to previousstudies, we found a higher incidence of pregnancy complicationsafter MFPR compared with spontaneous twins, especially PMC andPIH.     

Multiple pregnancy induction and selective fetal reduction in high genetic risk couples

Couples at risk for an inherited disorder often have severalpregnancy interruptions because of affected fetuses and difficultyin achieving their desired family. We evaluated the efficiencyand acceptability of selective fetal reduction after chorionicvillus sampling (CVS) of multiple pregnancy induced by ovarianstimulation and gamete intra-Fallopian transfer (GIFT). Thisapproach has been offered to nine patients at risk of Mendeliandiseases and one patient carrier of reciprocal translocation.The acceptance has been very high (90%). One patient at riskof an autosomic recessive disease opted for artificial donorinsemination, one conceived spontaneously, and one was a poorresponder to ovarian stimulation. Seven patients actually underwenta single GIFT procedure with six achieving pregnancy (86%),all but two being a multiple pregnancy (67%). All pregnanciesconcluded uneventfully at term and newborns were alive and healthy.Prenatal diagnosis, including fetal karyotyping in all cases,was performed at 8.5–11.5 weeks of gestation and confirmedeither on amniotic fluid aspirated at reduction or at birth.The number of fetuses was reduced to one or two because thegenetic disease was present and/or to reduce the risk of prematuredelivery and improve the likelihood of successful pregnancy.The new approach seems to be highly effective and might be considereda practical and useful alternative to preimplantation geneticdiagnosis.     

Multifetal reduction of triplets to twins: a prospective comparison of pregnancy outcome

The aim of this study was to compare the outcome of triplets managed expectantly or by multifetal reduction to twins to assess the potential benefit of fetal reduction. The study design was prospective, comparative and monocentric and the study was conducted in a teaching hospital. Out of 148 women with triplets mostly obtained after infertility treatment, 83 were expectantly managed while 65 chose reduction to obtain twins. Main outcome measures were fetal loss before 24 weeks, premature deliveries before 28, 32 and 34 weeks, rate of low birthweight infants and neonatal and perinatal mortality rates. The fetal loss rate before 24 weeks did not differ between the ongoing group and the reduced group (6 versus 5.4%). Reducing triplets was associated with a significantly lower incidence of the following: prematurity before 28, 32 and 34 weeks (P < 0.001), low birthweight infants whose weights were under the third centile (P < 0.002) and infants whose weights were less than 1000, 1500 and 2000 g (P < 0.001). Neonatal (although apparently lower in the reduced group) and perinatal mortality did not significantly differ. Our results indicate that reduction of triplets to twins is effective to improve preterm birth and fetal growth.     

First trimester fetal reduction: its role in the management of twin and higher order multiple pregnancies

Multiple pregnancy may be the result of stimulated or non-stimulated,and of assisted or natural conception. As observed in the pastdecade, assisted conception technologies have significantlyincreased the prevalence of multiple pregnancy. The increasehas been much more marked for triplets and higher order births.Rates of perinatal mortality and fetal and maternal complicationsare higher in twins than in singletons, and the adverse outcomerises with increasing number of multiples. Unplanned multiplepregnancy may be felt to be emotionally and physically so stressfulan experience as to drive patients to refusal of pregnancy itself,or to want to reduce the number of fetuses to an acceptablestandard. Fetal reduction techniques have emerged as a veryeffective medical approach to improve pregnancy outcome anda key option of patients trying to carry a pregnancy to term.Multiple fetuses are most frequently heterozygotes; thereforethe risk of each of them being affected by a Mendelian diseaseor sporadic chromosomal aberration is an independent probability.Thus, the incidence of genetic defects in at least one fetusis increased and directly related to the order of multiples,and this makes it worthwhile to offer karyotyping of the fetus(es)to be spared, before the reduction procedure takes place. Whena multiple pregnancy is established, one may conclude selectivereduction is the most effective therapeutic approach for reducingrisks.     

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.     

Sequential genetic events leading to conjoined twins in a monozygotic triplet pregnancy

A rare case of conjoined twins in a triplet pregnancy is presented.Selective termination was attempted. After termination of thepregnancy, deoxyribonucleic acid fingerprinting revealed a monozygoticorigin for all three fetuses.     

A family history of twinning in relation to multiple implantation

BACKGROUND: A familial basis for dizygotic twinning is known for multipleovulation. However, for multiple implantation this remains unclear.In IVF/intracytoplasmic sperm injection (ICSI) ‘multipleovulation’ is artificially induced. If multiple implantationis not hereditary, the incidences of twins in families of patientswith single and multiple implantation after IVF/ICSI with doubleembryo transfer (DET) should be comparable. METHODS: A questionnaire study was conducted among patients with intrauterine pregnancy at 6 weeks of gestation, after IVF/ICSI treatmentwith DET 3 days after oocyte retrieval. RESULTS: There were 940 patients who gave their informed consent. Forwomen with single implantation (Group A), the incidence of oneand of multiple twins among the family was 27.2 and 15.5%, respectively.For women with multiple implantation (Group B), this incidencewas 29.5 and 17.8%, respectively, P = 0.424. The incidence ofone and of multiple twins among first degree relatives was 10.6and 1.1% in Group A; for Group B this was 8.7 and 1.9%, P =0.469. Multivariate regression analysis also did not reveal‘twins in family’ or ‘twins in first degree’as an associated variable for multiple implantation at 6 weeks. CONCLUSIONS: Incidences of twins in families of patients with single implantationand patients with multiple implantation after IVF/ICSI are comparable.Our data do not support the concept that multiple implantationis hereditary.     

CASE REPORT: Severe ovarian hyperstimulation syndrome, selective embryo reduction and heterotopic pregnancy

Ovarian hyperstimulation syndrome is common (21.4%) in patientswith polycystic ovarian disease, treated by gonadotrophins.It is much frequent (50%) in conceptual cycles. We report acase associated with a quadruplet pregnancy that underwent selectiveembryo reduction at 8 weeks' gestation to a twin pregnancy andwas subsequently found to have an unruptured ectopic pregnancyat 11 weeks' gestation. After laparotomy and partial salpingectomya successful twin pregnancy ensued.     

Heterotopic Caesarean scar pregnancy combined with intrauterine pregnancy successfully treated with embryo aspiration for selective embryo reduction: case report

Ectopic pregnancy situated in a Caesarean section scar is a rare but potentially life-threatening event. Because of its rarity, there are no universal treatment guidelines to manage this condition. We report a case of IVF-induced triplet heterotopic pregnancy of early gestational age that included one Caesarean scar pregnancy diagnosed as early as 6 weeks gestation. Treatment with embryo aspiration under vaginal ultrasonography for selective embryo reduction was given and the concurrent intrauterine twin pregnancy was preserved successfully.     

体外受精-胚胎移植后三胎妊娠减胎术后随访结局分析

目的探讨体外受精-胚胎移植（IVF-ET）技术中减胎技术对于妊娠结局的影响。方法回顾性分析2005.01-2008.06期间于我中心接受IVF-ET治疗后三胎妊娠减为双胎妊娠33例（A组）及同期治疗获双胎妊娠69例（B组）随访资料,比较两组的流产率、早产率及新生儿出生胎龄、体重、围生儿死亡率等。结果流产率A组27.3%,B组15.9%;平均出生胎龄A组（36.4±2.4）周,B组（36.4±2.8）周;围生儿死亡率A组8.3%,B组6.0%,两组比较差异无显著性（P〉0.05）。早产率A组29.2%,B组25.9%,两组比较差异有显著性（P〈0.05）;平均出生体重A组（2386±602）g,明显低于B组（2586±595）g（P〈0.05）;出生体重〈1500g的比例A组10.4%,B组8.6%,两组比较差异有显著性（P〈0.05）。结论三胎妊娠早期行减胎术存在早产及低出生体重儿出生的可能性,选择适宜的移植胚胎数目,减少多胎妊娠的发生,才是预防不良妊娠结局的有效途径。     

Successful outcome of multifetal reduction in a pregnancy with 12 live fetuses

Multifetal reduction of 12 live fetuses enabled the successfuldelivery of a healthy pretern baby in a patient treated withhuman menopausal gonadotrophin/human chorionic gonadotrophin.     

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.     

Marked variation in antiphospholipid antibodies during pregnancy: relationships to pregnancy outcome.

Variations in blood concentrations of antiphospholipid antibodies (APA) were investigated through the course of pregnancy in women who had a history of recurrent pregnancy loss, and were related to changes in pregnancy outcome. Serial measurements of APA were made in 16 women with antiphospholipid syndrome (APS) and 16 with negative APA tests pre-pregnancy. There was considerable intraindividual variation in test results through pregnancy. There was a significantly higher ratio of dilute Russell's viper venom time and IgG ACA titre in the first trimester compared with results pre-pregnancy in women with APS. Furthermore, transiently positive APA results were noted in the control group during pregnancy and some women with antiphospholipid syndrome tested negative for APA in mid- and late pregnancy. We have demonstrated clinically important variations in the results of tests for APA during pregnancy in women with APS.     

Follicular diameters in conception cycles with and without multiple pregnancy after stimulated ovulation induction

BACKGROUND: Controlled ovulation induction and intrauterine insemination (OI-IUI) is associated with multiple pregnancies, which are a cause of much concern. No reliable datasets have shown clear criteria for predicting multiple pregnancy. The aim of this study was to eliminate a number of variables by examining only conception cycles to determine ultrasound criteria posing risks of multiple pregnancy. METHODS: 112 OI-IUI conception cycles (multiple pregnancy rate 19.6%) were analysed retrospectively to identify factors that may be used to evaluate multiple pregnancy risk. Analyses of ultrasound data on the day of hCG administration allowed study of the role of primary, secondary and tertiary follicle diameters (FD). RESULTS: There were no multiple pregnancies in cases where there was a single FD > or = 14 mm, and no higher-order pregnancies where the tertiary follicle measured <14 mm. Follicles with an FD of 15 mm showed an 8% attributable implantation rate. CONCLUSIONS: Revision of the criteria for administration of the ovulatory dose of hCG should include the concept that follicles of 15 mm diameter may yield a pregnancy. We suggest that rigorous application of such criteria (critical FD of 16 mm combined with secondary FD evidence) will not reduce the programme pregnancy rate, but will reduce the incidence of multiple conceptions.     

Infertility: The desire for multiple births in couples with infertility problems contradicts present practice patterns

Paradoxically, the attitude of infertility patients towardsmultiple births has never been investigated. We therefore generateda survey by questionnaire, which was sent to 3800 consecutiveunselected couples with infertility problems: 582 responseswere received (15% response rate) and analysed. The percentagedistribution of the responses to 21 questions, addressing attitudestowards and knowledge about the risk of multiple gestations,was the main outcome. Worry about multiple births was expressed,independent of the number of multiples, although fear aboutmultiple conceptions was rejected by a large majority (64%).The risk of a twin birth was not strongly perceived, but theperception of risk increased with increasing numbers of multiples:triplets (50–62%), quadruplets or more (71–72%).A desire for the conception of twins was expressed by 67–90%of couples, a desire for the conception of triplets was equallyexpressed and rejected, and for a multiple gestation beyondtriplets was rejected by 73–82% of couples. Patients wereeducated about the risks of selective embryo reduction and respondedin a bimodal fashion to the option of utilizing this procedure,with equal numbers being willing to consider or reject it. Age,parity and length of infertility did not affect the couples‘worry or fear about multiples. The desire for twins and triplets,however, was correlated significantly with age (twins, P = 0.032;triplets, P = 0.03); there was no such correlation for largermultiples. The length of infertility was correlated with a positiveattitude towards multiples beyond triplets (P = 0.029) but wasnot correlated with a desire for twins or triplets. Prior paritydid not affect the attitude towards multiples at all. The lengthof infertility was also correlated significantly to an understandingof risk (twins, P = 0.034; triplets, P = 0.001; quadrupletsand more, P = 0.05), while age and parity was not. The considerationof selective embryo reduction as a treatment option was correlatedsignificantly with age (P = 0.0001), while the understandingof associated risks was evenly distributed, independent of patientcharacteristics. We conclude that infertility patients appearto be educated about the risks of multiple births. A strongdesire for multiple births, as long as this can be limited totriplets or less, increases with advancing female age. Increasinglength of infertility, however, increases the willingness formultiples beyond triplets. Increasing female age increases thereadiness to consider selective embryo reduction as a treatmentoption. Attitudes do not differ between couples with primaryand secondary infertility. Patient attitudes are thus not inagreement with the existing practice patterns in infertilitytherapy. A re-evaluation of some of these practice patternsmay therefore be indicated.     

Avoiding multiple pregnancies in ART: multiple pregnancies: a test case for the moral quality of medically assisted reproduction

Although most professional societies have issued guidelines to diminish the number of embryos to be transferred during assisted reproduction techniques, the incidence of multiple pregnancies remains unacceptably high. The negative psychological, social and medical consequences for the patients and their offspring easily outweigh the benefits in terms of increased success rates. Multiple pregnancies would never be tolerated if the 'best interest of the child' standard was applied as strictly to these consequences, as it is to controversial family forms. The persistence of high multiple pregnancy rates is largely due to the pressure brought to bear on the physicians to increase the overall success rate. The fertility specialist should inform the patients about the risks and benefits of a multiple transfer but ultimately the specialist should decide how many embryos to transfer. Multifetal reduction is an ethically acceptable solution if, and only if, the physician has taken all reasonable steps to prevent the occurrence of a multiple pregnancy. Finally, an additional strategy to decrease the incidence of multiple pregnancies is proposed, i.e. to extend the professional responsibility of the fertility specialist to all steps of procreation including pregnancy, birth and neonatal care.     

The desire for multiple pregnancy in male and female infertility patients

BACKGROUND: It is apparent that many fertility patients consider multiple birth an ideal treatment outcome. We wished to evaluate the desire for multiple birth among patients, and the effect of patient demographics and recognition of the increased fetal risks of multiple pregnancy on this desire. METHODS: This was a prospective questionnaire study completed by 801 male and female infertility patients attending a tertiary level Canadian university fertility clinic. Two logistic regression analyses were performed with desire for multiple birth with next fertility treatment and recognition of the increased fetal risks of multiple pregnancy as the dependent variables. RESULTS: 41% of patients desired a multiple birth. Increasing duration of infertility or previous assisted reproductive treatment increased, and having previous children or recognition of the increased fetal risks decreased, this desire. Patient age or sex did not affect desire for multiple birth. Previous assisted reproductive treatment was associated with increased recognition of the fetal risks of multiple pregnancy. CONCLUSIONS: A significant proportion of fertility patients considers multiple birth an ideal treatment outcome. Recognition of the increased fetal risks of multiple pregnancy significantly reduced this desire. Patient education may play an important role in assisting physicians in the quest to reduce the contribution of assisted reproductive treatment to multiple births and their attending complications.     

The implantation of every embryo facilitates the chances of the remaining embryos to implant in an IVF programme: a mathematical model to predict pregnancy and multiple pregnancy rates

BACKGROUND: We aimed to assess the validity of a theoretical mathematical model to predict the pregnancy rate and the multiple pregnancy rate in IVF/oocyte donation programmes on the basis of the implantation rate and the number of transferred embryos. METHODS: A total of 1835 embryo transfers corresponding to three different programmes in two centres with different implantation rates were analysed. Pregnancy and multiple pregnancy rates observed in the aforementioned programmes were compared with those obtained following different mathematical models. Four models were tested: binomial model, ground model, maternal variability model and collaborative model. The goodness of fit was performed by means of the maximum likelihood fit method. RESULTS: The binomial model could not predict the pregnancy rate, and especially the multiple pregnancy rate. The multiple pregnancy rate predicted following the binomial model was much lower than observed, up to 40-fold reduced. Ground model and maternal variability model adjusted to the data with more precision, but were still not accurate. Finally, the collaborative model reproduced with very great accuracy both pregnancy rate and the multiple pregnancy rate. A collaborative parameter of 22% was found, implying that the implantation probability of each embryo is increased by 22% for every embryo previously implanted. CONCLUSIONS: Embryonic implantation does not follow a binomial law, showing that the implantation is not independent from the number of embryos implanted. The best fit to the data is obtained following a collaborative model by which the implantation of one embryo is facilitated by the implantation of other embryo(s). The mathematical formula of the collaborative model predicts very accurately the pregnancy rate and the multiple pregnancy rate in IVF/oocyte donation programmes, based on the implantation rate of this specific programme and the number of embryos transferred up to five embryos. We recommend using the aforementioned formula to quantify the pregnancy rate and the risk of multiple pregnancy in the counselling of the infertile couple at embryo transfer. Such a formula is freely available at www.ifca.unican.es/matorras/mathpreg/.     

Mutation and haplotype analysis for Duchenne muscular dystrophy by single cell multiple displacement amplification

Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder with mutational heterogeneity. The scarcity of DNA from single cells in preimplantation genetic diagnosis (PGD) for DMD limits comprehensive genetic testing. Multiple displacement amplification (MDA) is reported to generate large amounts of template and give the most complete coverage and unbiased amplification to date. Here, we developed mutation and haplotype analysis in conjunction with gender determination on MDA products of single cells providing a generic approach that widens availability of PGD for female carriers with varied mutations. MDA amplified with 98.5% success for single lymphocytes and 94.2% success for single blastomeres, which was evaluated on 60 lymphocytes and 40 blastomeres. A total of six commonly mutant exons, eight short tandem repeat markers within dystrophin gene and amelogenin were incorporated into subsequent singleplex PCR assays. The mean allele dropout rate was 9.0% for single lymphocytes and 25.5% for single blastomeres. None of the blank controls gave a positive signal. Genotyping of each pedigree for three families provided 2-3 fully informative alleles per dystrophin haplotype besides specific mutant exons and amelogenin. We suggest that this approach is reliable to identify non-carrier female embryos other than unaffected male embryos and reduce the risk of misdiagnosis.     

Genetic susceptibility to multiple sclerosis: a linkage analysis with age-of-onset corrections

To test the hypothesis that a multiple sclerosis susceptibility (MSS) gene is linked to the HLA loci, formal linkage analysis was conducted on 40 multiplex families, 20 each from the Seattle and Los Angeles areas. The computer program LIPED was utilized. A dominant model of inheritance was assumed. Penetrance values of 0.05, 0.35, and 0.67 were entered into the analyses, and an age-of-onset correction was incorporated. The resulting lod scores were supportive of linkage at the lower penetrance levels. The maximum lod score, 2.411, at an estimated recombination fraction of 0.10 in both males and females, was generated at a penetrance value of 0.05. With a penetrance value of 0.67, the lod scores did not support linkage.
Under an autosomal dominant model of inheritance, the results were supportive of linkage when the presumed penetrance of the MSS gene is low. The results also confirmed the importance of incorporating an age-of-onset correction into linkage analyses.