Selective reduction of multifetal pregnancies in the first trimester using colour Doppler ultrasonography

In pregnancies with multiple gestation, an adverse outcome isdirectly proportional to the number of fetuses within the uterus,primarily because of an increased predisposition to prematuredelivery. Although there is a good deal of information aboutmultifetal reduction in triplets and quadruplets and even quintuplets,there is very little on sextuplets, and virtually nothing onseptuplets. Among the different techniques proposed for selectivetermination, two approaches have been more widely adopted: transcervicalaspiration and transabdominal needling of the embryo using greyscale ultrasonography, but as yet there is no report on multifetalreduction using colour Doppler ultrasound. A method for selectivetermination of multiple pregnancy using transabdominal colourDoppler ultrasonography has been described here for the firsttime in a case of septuplets.     

The physical and mental development of co-sibs surviving selective reduction of multifetal pregnancies

Fetal reduction in humans is still controversial and considered exploratory. The medical, legal and ethical issues involved have been widely discussed, yet, the long term effects on the surviving co-sibs have not been documented. We report on the psychomotor and physical development of seven children born following fetal reduction in three women, initially bearing 13 fetuses altogether. To these children we matched controls for birth weight, gestational age, sex, mode of delivery, parity, age at examination and mother's age and education. The children's age at evaluation varied between 12.5 and 38 months. It was found that the mental and physical indices of these children did not differ from their matched controls. It is our belief that reduction of pregnancies of high fetal order into pregnancies of low fetal order is medically acceptable.     

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 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.     

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.     

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.     

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.     

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.     

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.     

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.     

The influence of the depth of embryo replacement into the uterine cavity on implantation rates after IVF: a controlled, ultrasound-guided study

BACKGROUND: Traditionally, embryo transfer after IVF has been performed blindly and placing the embryos approximately 1 cm below the fundal endometrial surface. However, it has been suggested that transferring embryos rather lower in the uterine cavity or high in the uterus may improve implantation rates. Nevertheless, there has not yet been a controlled trial to prove this theory. This prospective randomized study investigates the influence of the depth of embryo replacement on the implantation rate after embryo transfer carried out under transabdominal ultrasound guidance. METHODS: A total of 180 consecutive patients undergoing ultrasound-guided embryo transfer were randomized to three study groups according to the distance between the tip of the catheter and the uterine fundus at the moment of the embryo deposition in the lumen of the endometrial cavity: group 1: 10 +/- 1.5 mm; group 2: 15 +/- 1.5 mm; group 3: 20 +/- 1.5 mm. RESULTS: There was equal distribution between all three study groups regarding the main demographic and baseline characteristics of the patients, ovarian response, oocyte retrieval and IVF outcome, as well as the characteristics of embryo transfer and luteal phase support. The position of the catheter tip in relation to the fundal endometrial surface in groups 1 (10.2 +/- 0.9 mm), 2 (14.6 +/- 0.7 mm) and 3 (19.3 +/- 0.8 mm) was significantly different. Implantation rate was significantly higher (P < 0.05) in groups 2 (31.3%) and 3 (33.3%) compared with group 1 (20.6%). CONCLUSIONS: The depth of the embryo replacement into the uterine cavity may influence implantation rates, and thus it should be considered as an additional procedure among factors recently proposed as associated with successful embryo transfer after IVF.     

Surgery: A successful in-vitro fertilization and embryo transfer treatment in a woman with previous vaginoplasty for congenital absence of vagina

A mock embryo transfer under ultrasound guidance helped to planan embryo transfer in a woman with previous vaginoplasty.     

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.     

Successful non-surgical management of a heterotopic abdominal pregnancy following embryo transfer with cryopreserved-thawed embryos.

Heterotopic pregnancy is an increasingly common complication of assisted reproductive technology. Abdominal pregnancy is a rare and life-threatening form of ectopic pregnancy that can present as the extrauterine portion of a heterotopic pregnancy. We present the case of a cryopreserved-thawed embryo transfer that resulted in a simultaneous intrauterine and abdominal pregnancy first recognized at 10 weeks gestation. Ultrasound-guided transvaginal injection of potassium chloride into the abdominal pregnancy resulted in asystole and spontaneous resorption of the ectopic fetus, while the intrauterine pregnancy continued and resulted in a liveborn vaginal delivery at full term. Selective embryo reduction using a non-surgical approach in a haemodynamically stable patient can therefore be considered in the management of heterotopic abdominal pregnancy if diagnosed relatively early.     

Stronger reduction of assisted reproduction technique treatment cycle numbers in economically weak geographical regions following the German healthcare modernization law in 2004

BACKGROUND: As part of the German healthcare modernization law implemented in 2004, infertile couples face a 50% co-payment of the total assisted reproduction technique (ART) treatment costs. This has led to a drastic reduction in ART treatment cycle numbers after January 2004. The hypothesis tested in the present study was that the number of ART treatment cycles in different German federal states changed differentially after implementation of the law, depending on the economical power of the individual state in terms of gross domestic product per capita (GDP pc). METHODS: This was a retrospective data exploratory study. Data from the German IVF registry and the German Federal Statistics Office were utilized. Main outcome parameter was the proportional difference of ART treatment numbers between the time periods 2002-2003 and 2004-2005 stratified for the 16 German federal states. The federal states were grouped by Tukey-Hinges percentile analysis of GDP pc. RESULTS: The reduction of ART treatment cycle number was strongest in the lowest GDP pc group of federal states (Kruskal-Wallis P = 0.038). Mean reduction in ART cycle numbers was 51.5%, 35.7% and 38.8% in the 0-25th, 25-75th and 75-100th GDP pc percentile group, respectively. CONCLUSIONS: Conclusively, reduction in ART treatment cycle numbers following the German healthcare modernization law was significantly stronger in economically weak geographical regions.     

Risks and complications in assisted reproduction techniques: Report of an ESHRE consensus meeting

Assisted reproduction technique (ART) is an efficacious treatment in subfertile couples. So far little attention has been paid to the safety of ART, i.e. to its adverse events and complications. The consensus meeting on Risks and Complications in ART held in Maastricht in May 2002 focused on four topics: multiple pregnancies, long-term effects of ART on women, effects of ART on offspring, and morbidity/mortality registries.     

Ectopic pregnancies in Caesarean section scars: the 8 year experience of one medical centre

BACKGROUND: Our aim was to supplement the mostly individual case reports on the rarely occurring and life-threatening condition of ectopic pregnancy developing in a Caesarean section scar. METHODS AND RESULTS: Eight of all the patients treated in our department between 1995 and 2002 had been diagnosed for ectopic pregnancy that developed in a Caesarean section scar. They comprised this case series group. Four of them underwent methotrexate treatment; one had expectant management, one transcervical aspiration of the gestational sac and two by open surgery. All the non-surgically treated women had an uneventful outcome. One underwent a term Caesarean hysterectomy and the other first trimester hysterotomy and excision of the pregnancy located in the scarred uterus. Analysis of all these women's obstetric history revealed that five of them (63%) had been previously operated because of breech presentation, one had a cervical pregnancy and one had placenta previa. Four of them (50%) had multiple (> or = 2) Caesarean sections. CONCLUSIONS: The women at risk for pregnancy in a Caesarean section scar appear to be those with a history of placental pathology, ectopic pregnancy, multiple Caesarean sections and Caesarean breech delivery. Heightened awareness of this possibility and early diagnosis by means of transvaginal sonography can improve outcome and minimize the need for emergency extended surgery.     

Diagnostic Techniques: Magnetic resonance imaging and transvaginal ultrasound of the uterus prior to embryo transfer

This study was designed to investigate the role of magneticresonance (MR) imaging in predicting the outcome of in-vitrofertilization (IVF)/embryo transfer treatment by seeking differencesin receptive compared to unreceptive endometria. Women aboutto undergo embryo transfer were submitted to both vaginal ultrasoundand MR imaging. Measurements were obtained of the thickness,cross-sectional area and volume of uterine layers and of theMR signal intensity ratios between layers. Measurements werecompared with the occurrence of subsequent successful implantation.Although there was no association with either the quantity orthe relative signal intensity of the endometrium, an interdependencewas demonstrated between both the endometrium/ myometrium andmyometrium/ junctional zone signal intensity ratios and subsequentsuccessful implantation (P < 0.037 and < 0.004 respectively).It is concluded that MR imaging may provide unique informationwhich may help in predicting the outcome of IVF/embryo transfertreatment and in understanding implantation. Significant differenceswere seen in the relative MR signal intensities of the myometrium     

Successful management of a heterotopic Caesarean scar pregnancy: potassium chloride injection with preservation of the intrauterine gestation: case report

Caesarean scar pregnancy (CSP), in which the pregnancy is located in the scar of a previous Caesarean section, is a rare situation that carries a high risk of uterine rupture. Improved ultrasound imaging allows early diagnosis of this condition, but there is no standard management. We report the first case of CSP associated with a normal intrauterine pregnancy. Potassium chloride administered under transvaginal ultrasonographic guidance terminated cardiac activity in the CSP. The CSP resolved, and a healthy infant was delivered at 36 weeks. When the diagnosis is early and the patient asymptomatic, surgery can be avoided, the CSP can be terminated selectively and the intrauterine pregnancy thereby preserved.     

Immunological testing and treatment in reproduction: frequency assessment of practice patterns at assisted reproduction clinics in the USA and Australia

BACKGROUND: The roles that alloimmunity and autoimmunity may play in reproductive failure, including recurrent pregnancy loss and failed IVF, have not been clearly established. To help define practice patterns, we investigated what tests clinicians in the USA and Australia were offering, to which patients (diagnostic groups) the tests were recommended, and in what situations immunological/anticoagulation treatment was advised. METHODS: A five section survey was completed by senior physicians attending the annual national fertility society meetings in the USA and Australia. Results were tabulated and analysed. RESULTS: Antiphospholipid antibody testing was offered to patients with recurrent pregnancy loss by almost all physicians surveyed. Patients with previous failure of IVF were tested much less often. Other immune tests (embryotoxic assay, natural killer cells and leukocyte antibodies) were ordered by none of the Australian participants and approximately 25% of the American participants. The use of immunotherapy and anticoagulation therapy for patients who tested positive for various immunological tests was also evaluated for frequency of use and reported secondary complications. CONCLUSIONS: Large, well-structured studies examining the benefits of immunological evaluation and treatment are necessary before definite recommendations can be made.