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 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.     

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).      

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.     

The management of multiple pregnancies after induction for superovulation

The high rate of multiple pregnancies after embryo transferdepends upon the number of embryos replaced and amounts to {smalltilde}20% for four or more embryos. This incidence justifiesa preventive or curative treatment after the induction of superovulation.Aspiration of one or more embryos via the cervix under ultrasoundcontrol has been undertaken on 42 patients since 1983, and involvedtwo sextuplets, 10 quadruplets, 18 triplets and 12 twins. Twentysix embryo reductions were performed before 9 weeks of amenorrhoea.Five failures after 9 weeks were due, in the early stages ofthis procedure, to infection. In the case of twins, the indicationwas a scarred uterus in 10 cases and a psychiatric reason fortwo patients. In 19% of our cases delivery occurred within 32weeks of amenorrhoea.     

Prenatal sonographic diagnosis of a fetal renal mesoblastic nephroma occurring after transfer of a cryopreserved embryo.

Here we report the first case of prenatally diagnosed fetal renal mesoblastic nephroma occurring after transfer of a cryopreserved embryo. A 37 year old woman, having immunological infertility, was treated by in-vitro fertilization (IVF) and embryo transfer. Following unsuccessful IVF using fresh embryos, the patient conceived after transfer of cryopreserved-thawed embryos. The chromosomal analysis identified a normal karyotype at 16 weeks' gestation when amniocentesis was performed. The pregnancy course was uneventful until 28 weeks' gestation when polyhydramnios associated with fetal renal tumour was detected using ultrasonography. A male infant weighing 2564 g was born via Caesarean section at 34 weeks' gestation. A left nephrectomy was performed 5 days after delivery and the tumour was identified histologically as a mesoblastic nephroma. The postoperative course was uncomplicated to this point.     

Conversion of cycles involving ovarian hyperstimulation with intra-uterine insemination to in-vitro fertilization

Conversion to in-vitro fertilization (IVF) and embryo transferas an alternative to cancellation was offered in 27 consecutivecycles of controlled ovarian hyperstimulation and intra-uterineinsemination (IUI) cycles with excessive follicular developmentin patients with idiopathic infertility. IVF and embryo transferwas performed in 25 cycles, resulting in 13 pregnancies (52%),with 22% of couples having at least two embryos cryopreserved.The pregnancies have resulted in one singleton and two twinbirths, one spontaneous abortion, and nine ongoing pregnancies(including one triplet gestation). Four patients developed severeovarian hyperstimulation syndrome (OHSS) after IVF and embryotransfer, including two cases requiring paracentesis. Threeof four OHSS patients were pregnant, resulting in live birthsof healthy twins, one spontaneous abortion and one ongoing singletongestation. In two cycles a spontaneous luteinizing hormone (LH)surge occured, preventing oocyte retrieval. For these two women,drainage of all follicles except the five most likely to fertilize(18–22 mm diameter) was performed, followed by IUI, withno pregnancies or OHSS observed. Conversion of patients fromIUI cycles to IVF/embryo transfer cycles avoids cancellationof the very cycles with the best chance of achieving pregnancy.OHSS remains a problem, necessitating extensive pre-IVF counsellingand post-transfer vigilance.     

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

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

Prenatal diagnosis of a complete mole coexisting with a dichorionic twin pregnancy: case report

A complete mole coexisting with dichorionic twins was diagnosed by the combined use of sonography and chorionic villus sampling at 10 weeks gestation. The pregnancy resulted in the death of one fetus at 31 weeks from presumed feto-maternal haemorrhage, while the other fetus survived in good condition. A summary of the available literature, combined with this report, reveals a total of seven pregnancies with twins and a coexistent complete mole. Only two out of 14 fetuses survived. Maternal complications included one case of pre-eclampsia and one persistent trophoblastic tumour. Accurate diagnosis of complete mole is possible by genetic analysis of chorionic villi obtained with standard transabdominal sampling. Twins with a coexistent complete mole will usually undergo miscarriage. However, fetal survival is possible and the maternal risks seem limited. A concomitance between gestational trophoblastic disease and the occurrence of feto-maternal haemorrhage is observed.     

Obstetric outcome of 424 pregnancies after intracytoplasmic sperm injection

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

Clinical outcomes following interval laparoscopic transabdominal cervico-isthmic cerclage placement: case series

The purpose of this report is to describe outcomes following laparoscopic transabdominal cervico-isthmic cerclage placement in cases of cervical incompetence not amenable to a conventional transvaginal procedure. We reviewed records of the first 11 patients at an academic teaching hospital who underwent laparoscopic transabdominal cerclage placement as an interval procedure, using a technique we previously first described. For all patients, the clinical course, including surgical complications and outcome of all subsequent pregnancies, is briefly described. One case was complicated by a small bowel injury secondary to concomitant extensive enterolysis. Otherwise there were no complications. Mean estimated blood loss was <40 ml. To date, 10 patients have conceived a total of 12 pregnancies following the procedure. Two pregnancies resulted in spontaneous losses at 8 weeks gestation, two in deliveries by Caesarean section at 34.5 weeks, and eight in deliveries by elective Caesarean section at 38 weeks or more. Each delivery resulted in the birth of a healthy infant. In conclusion, patients who require a transabdominal cerclage may undergo a laparoscopic interval procedure and achieve outcomes similar to those following placement via laparotomy during pregnancy.     

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.     

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.     

Pregnancy: Heterotopic pregnancies after in-vitro fertilization and embryo transfer

A total of 20 cases of heterotopic pregnancy were encounteredamong 2650 clinical pregnancies (0.75%) resulting from in-vitrofertilization/embryo transfer at Bourn Hall Clinic (Cambridge,UK) during the period July 1984-July 1993. The aetiology ofheterotopic pregnancy in the series is multifactorial, withtubal damage as the main factor. Transvaginal ultrasonographyshowed a high sensitivity for making correct diagnoses of heterotopicpregnancies compared with transabdominal ultrasonography (93.3versus 50.0%). The mean plasma human chorionic gonadotrophin(HCG) concentration on day 13 after embryo transfer was similarto those of uncomplicated intrauterine pregnancies and hencewas of no diagnostic value. The serial plasma HCG concentrationsof patients who delivered were significantly higher than forthose who aborted their intrauterine pregnancies (P < 0.01),although the sample of data available was too small to makefirm inferences. It does appear that serial HCG concentrationsmay have a predictive value of fair accuracy regarding the outcomeof the intrauterine pregnancy in heterotopic pregnancies. Theclinical presentations of the 20 cases at first examinationwere quite variable, with 45% (9/20) of patients asymptomatic.Tubal pregnancy in one patient resolved spontaneously, two caseswere treated by an injection of potassium chloride into thegestational sac and the remaining 17 cases were treated by salpingectomy.In 10 patients the intrauterine pregnancy resulted in live birthand the remaining 10 patients aborted spontaneously.     

Uterine rupture following hysteroscopic lysis of synechiae due to tuberculosis and uterine perforation

A patient with genital tuberculosis who conceived with in-vitrofertilization and embryo transfer following hysteroscopic synechiolysiscomplicated by a fundal uterine perforation subsequently presentedwith uterine rupture at 36 weeks gestation. Immediate Caesareansection and repair of the ruptured uterus were performed. Womenwith a history of uterine perforation should be counselled regardingthe risk of uterine rupture during their subsequent pregnancies.     

42例孕妇孕早期绒毛组织细胞遗传学分析

目的评价早孕期B超引导下经腹绒毛取材组织样本的细胞遗传学分析在产前诊断中的应用价值。方法回顾分析2010年1月到2011年6月42例早孕期产前细胞遗传学诊断的病例资料。结果 42例取材时间9～13周,穿刺成功率100%,培养成功率为97.6%,平均培养时间为10天,发现异常核型4例。结论孕9周后行B超引导经腹绒毛取材是一项安全可行的早孕期介入性产前诊断方法。绒毛细胞长期培养法和染色体制备方法简单、技术稳定、结果可靠,可用于胎儿染色体疾病的产前诊断。     

Quintuplet pregnancy following transfer of two blastocysts: Case report

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

Transabdominal embryofetoscopy for the detection of short rib-polydactyly syndrome, type II(Majewski), in the first trimester

Our aim was to demonstrate the potential of first-trimester embryofetoscopy for prenatal diagnosis in a continuing pregnancy. A patient at risk for giving birth to an infant with short rib-polydactyly syndrome, type II (Majewski), presented for prenatal diagnosis at 9 weeks of gestation. A 1 mm semirigid fiberoptic endoscope with an 18 gauge examination sheath and a single-chip digital camera were used for transabdominal embryofetoscopy. Transabdominal embryofetoscopy was performed at 13 weeks of gestation. Direct visualization of the fetus was achieved and no gross limb or facial abnormalities were seen. This case shows that embryofetoscopy is a useful tool for early diagnosis in high-risk patients in the first trimester for continuing pregnancies.     

Monozygotic twin delivery following reduction from quadramniotic-dichorionic gestation established after ICSI and embryo transfer: Case report

We report the delivery of healthy monozygous (MZ) twins in a 31 year-old nulligravida following gonadotrophin ovulation induction, ICSI, assisted hatching and fresh embryo transfer. Although a sonogram on day 35 confirmed that two of four transferred embryos had implanted, a second transvaginal sonogram 1 week later showed each gestational sac had two conceptuses-all four were associated with distinct amniotic compartments. Cardiac activity was observed in all four embryos. At 12 weeks and 5 days gestation, chorionic villus sampling was performed on fetuses 1 and 2 which were euploid for chromosomes 13, 18, 21, X and Y via fluorescence in-situ hybridization analysis. Subsequent KCl injection into sacs 3 and 4 resulted in asystole for these fetuses, while cardiac activity in sacs 1 and 2 remained unchanged after reduction. A twin vaginal delivery occurred at 36 weeks gestation, resulting in the birth of two male infants and one placenta. This case represents the first known report of human quadruplet pregnancy consisting of two MZ twin sets conceived by assisted reproductive techniques. Our report reviews proposed mechanisms for explaining twinning, with special emphasis on zona pellucida micromanipulation and subsequent MZ twin induction.     

Prevention of twin pregnancy after in-vitro fertilization or intracytoplasmic sperm injection based on strict embryo criteria: a prospective randomized clinical trial.

A prospective randomized study comparing single embryo transfer with double embryo transfer after in-vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) was carried out. First, top quality embryo characteristics were delineated by retrospectively analysing embryos resulting in ongoing twins after double embryo transfer. A top quality embryo was characterized by the presence of 4 or 5 blastomeres at day 2 and at least 7 blastomeres on day 3 after insemination, the absence of multinucleated blastomeres and <20% cellular fragments on day 2 and day 3 after fertilization. Using these criteria, a prospective study was conducted in women <34 years of age, who started their first IVF/ICSI cycle. Of 194 eligible patients, 110 agreed to participate of whom 53 produced at least two top quality embryos and were prospectively randomized. In all, 26 single embryo transfers resulted in 17 conceptions, 14 clinical and 10 ongoing pregnancies [implantation rate (IR) = 42.3%; ongoing pregnancy rate (OPR) = 38.5%] with one monozygotic twin; 27 double embryo transfers resulted in 20 ongoing conceptions with six (30%) twins (IR = 48.1%; OPR = 74%). We conclude that by using single embryo transfer and strict embryo criteria, an OPR similar to that in normal fertile couples can be achieved after IVF/ICSI, while limiting the dizygotic twin pregnancy rate to its natural incidence of <1% of all ongoing pregnancies.