Effects of fetal number and multifetal reduction on length of in vitro fertilization pregnancies

OBJECTIVE: To determine the effects of multifetal reduction and other variables on the duration of gestation of in vitro fertilization (IVF) pregnancies. METHODS: All 274 IVF pregnancies from the inception of the Women and Infants' Hospital IVF Program on May 26, 1988, until December 31, 1993, were evaluated. RESULTS: Spontaneous reduction occurred in ten pregnancies, and multifetal reduction was elected in 28 multiple gestations. Among 260 pregnancies that remained viable beyond 20 weeks, 162 singletons (37.9 +/- 0.29 weeks; mean +/- standard error) had a longer mean gestation than did 64 twins (34.6 +/- 0.61 weeks), 25 pregnancies reduced to twins (33.4 +/- 1.0 weeks), or nine triplets (29.7 +/- 1.9 weeks). Triplets delivered 4.9 weeks earlier than nonreduced twins (P < .05) and 3.7 weeks before twins resulting from multifetal pregnancy reduction (P < .05). Regression analysis showed that at the 8-week ultrasound, each viable fetus could be expected to reduce the duration of the gestation by about 3.6 weeks, and each fetus reduced medically or as a result of natural causes could be expected to prolong the gestation by approximately 3.0 weeks. Only 14% of triplet pregnancies underwent spontaneous multifetal reduction. CONCLUSION: Multifetal reduction of pregnancies with three or more fetuses was beneficial and increased the duration of gestation.     

Re: Second-trimester maternal serum alpha-fetoprotein, human chorionic gonadotropin, and unconjugated oestriol after early transvaginal multifetal pregnancy reduction

BACKGROUND: There is a certain amount of controversy regarding the need to divide the short gastric vessels (SGV) in laparoscopic fundoplication for treatment of gastroesophageal reflux disease (GERD). In addition, there is often difficulty in identifying the crural fibers when encircling the lower esophagus. METHODS: We determine whether it is necessary to divide the SGV by trying to appose the gastric fundus to the anterior abdominal wall intraoperatively. If this could be done easily, the SGV are preserved. When their division is required, a posterior gastric approach is employed. We have also found that the injection of methylene blue into the left crural fibers anterior to the esophagus is helpful in identifying the left side when dissection posterior to the gastroesophageal junction is difficult. RESULTS: Between 1992 and 1995 we performed 20 laparoscopic fundoplications for GERD. All patients had at least grade 3 esophagitis (Savary-Miller scale), increased esophageal exposure to acid (median DeMeester score of 195), and decreased lower esophageal sphincter (LES) pressure. The median operative time was 175 min. There were no conversions to open surgery, and there was no mortality. Three patients developed transient postoperative dysphagia and one patient had pneumonia. The median hospital stay was 3 days; all patients were free of reflux symptoms at follow-up ranging from 7 to 42 months. CONCLUSION: We conclude that the techniques described by us aid in intraoperative decision making and allow laparoscopic fundoplication to be both simple and effective.     

Probabilities for singleton and multiple pregnancies after in vitro fertilization

OBJECTIVE: To help physicians provide risk estimates for specific pregnancy outcomes. DESIGN: Computation of exact binomial probabilities for singleton and multiple pregnancies as a function of two inputs: the number of embryos transferred and the implantation rate. Inputs were varied over the range of values reported in the literature. MAIN OUTCOME MEASURE(S): Probabilities for a singleton pregnancy (none), a multiple pregnancy (Pmult), and no pregnancy (Pnone) after one IVF cycle. RESULT(S): Given a 30% implantation rate and three embryos transferred, Pone=.44, Pmult=.22, and Pnone=.34. Although further increasing the number of embryos transferred increases the chance of pregnancy, it also raises the probability of a multiple pregnancy and lowers the chance of a singleton pregnancy. Although varying the implantation rate changes the specific probability estimates, the same trade-off persists. CONCLUSION(S): Those who consider an IVF "success" to be a singleton pregnancy should be attentive to the number of embryos transferred. Infertility therapy may be one area in medicine where more is not necessarily better.     

Circulating maternal serum progesterone in high-risk pregnancies

Serum progesterone was measured by competitive protein-binding assay in 331 cases of normal pregnancy ranging from 6 to 42 weeks. Serial estimations of serum progesterone were performed in nine cases of severe hypertensive disorder of pregnancy, eight cases of twin pregnancy, three cases of twin pregnancy complicated by severe hypertensive disorder of pregnancy, three cases of triplet pregnancy, three cases of previous bad obstetric history, one case of anencephaly, and seven cases of intrauterine fetal death. Serum progesterone remained within normal range in severe hypertensive disorder of pregnancy and the levels were indistinguishable in cases of fetal growth retardation from those without growth retardation. In twin and triplet pregnancies, serum progesterone was within normal range or elevated and was usually higher than normal in twin pregnancies after weeks 33 to 34. Serum progesterone levels were normal in anencephalic pregnancy and in most cases of intrauterine fetal death. The findings are discussed with reference to placental hormonal activity. It is concluded that serum progesterone is a poor index of placental function.     

Children conceived by in vitro fertilisation after fresh embryo transfer

AIMS: To compare the outcome in in vitro fertilisation (IVF) children (after fresh embryo transfer) from multiple and singleton births with one another, and with normally conceived control children. METHODS: A cohort of 278 children (150 singletons, 100 twins, 24 triplets and four quadruplets), conceived by IVF after three fresh embryos had been transferred, born between October 1984 and December 1991, and 278 normally conceived control children (all singletons), were followed up for four years after birth. They were assessed for neonatal conditions, minor congenital anomalies, major congenital malformations, cerebral palsy and other disabilities. Control children, all born at term, were matched for age, sex and social class. RESULTS: The ratio of male:female births was 1.03. Forty six per cent of IVF children were from multiple births; 34.9% were from preterm deliveries; and 43.2% weighed less than 2500 g at birth. The IVF singletons were on average born one week earlier than the controls, weighed 400 g less, and had a threefold greater chance of being born by caesarean section. The higher percentage of preterm deliveries was largely due to multiple births and they contributed to neonatal conditions in 45.0% of all IVF children. The types of congenital abnormalities varied: 3.6% of IVF children and 2.5% of controls had minor congenital anomalies, and 2.5% of IVF children and none of the controls had major congenital malformations. The numbers of each specific type of congenital abnormality were small and were not significantly related to multiple births. IVF children (2.1%) and 0.4% of the controls had mild/moderate disabilities. They were all from multiple births, including two children with cerebral palsy who were triplets. CONCLUSIONS: The outcome of IVF treatment leading to multiple births is less satisfactory than that in singletons because of neonatal conditions associated with preterm delivery and disabilities in later childhood. A reduction of multiple pregnancies by limiting the transfer of embryos to two instead of three remains a high priority.     

Severe ovarian hyperstimulation syndrome and tubal pregnancy after in vitro fertilization

We report a case of a 38 year old woman with tubal pregnancy and severe ovarian hyperstimulation syndrome (OHSS) following in-vitro fertilization and intrauterine embryo transfer. The diagnostic and therapeutic problems in the coexistence of ectopic pregnancy and OHSS are discussed both in terms of the case-history and the literature.     

Ectopic pregnancy in the stump of the uterine tube after in vitro fertilization

A rare case of ectopic pregnancy in stump of uterine tube after IVF, which was done after bilateral removal of uterine tubes, caused by uterine tube pregnancies was described. Diagnostic difficulties were shown in that case.     

Follow-up of a cohort of 422 children aged 6 to 13 years conceived by in vitro fertilization

OBJECTIVE: To contact the total cohort of children conceived by IVF-ET consecutively in our center between June 1981 and December 1988. DESIGN: Retrospective study. SETTING: Infertility unit of the department of Obstetrics and Gynecology, Antoine Béclère Hospital, Clamart, France. PATIENT(S): Complete information was obtained on 370 children. The percentage lost for follow-up was 9%. INTERVENTION(S): To assess the children's well-being, telephone interviews of the parents and questionnaires sent to the parents and/or pediatrician were used. MAIN OUTCOME MEASURE(S): Surgical procedures, malformation, height and weight, school performance. RESULT(S): The physical growth of these children showed no major pathological features, with only 2.2% of them being below 2 SD for weight and 0.3% for height. The rates of malformation were not significantly different between these children and the general population. School performance was good, with 92.2% presenting encouraging outcome. Fifty-eight percent of the parents of children aged 6 to 10 years old did not inform their children about the IVF nor did 34% of the parents of children aged 11 to 13. Subsequent to the birth of the IVF child, 30 patients (8.9%) had a spontaneous pregnancy. However, five of them (15.1%) were ectopic. CONCLUSION(S): This study reports, for the first time, reassuring data on the long-term assessment of a large group of older IVF-ET children conceived consecutively, with a low percentage of subjects lost for follow-up.     

Cornual pregnancies in patients with prior salpingectomy undergoing in vitro fertilization and embryo transfer

OBJECTIVE: To examine the frequency of cornual pregnancy in patients with prior salpingectomy undergoing IVF. DESIGN: Review. SETTING: Private fertility practice. PATIENTS: Women undergoing IVF. MAIN OUTCOME MEASURE: Cornual ectopic pregnancy. RESULTS: Of 26 ectopic pregnancies detected after ET during a 7-year period, 7 were located in the cornu or tubal stump after prior salpingectomy. CONCLUSIONS: Patients with prior salpingectomy undergoing IVF are at particular risk for cornual pregnancy.     

First trimester maternal serum concentrations of fetal antigen 2 in normal pregnancies and those affected by trisomy 21

Serum concentrations of fetal antigen 2 (FA-2), the amino-propeptide of the alpha1 chain of collagen type I, were measured in peripheral blood from women with normal (n = 234) and trisomy 21 affected (n = 14) pregnancies between 9 and 11 weeks gestation. Serum FA-2 concentrations were seen to be stable throughout this period, and though raised FA-2 concentrations were seen at the 10th week of gestation, a statistically significant difference between normal and trisomy 21 affected pregnancies was not found overall. Therefore it seems unlikely that FA-2 has a role in first trimester screening for trisomy 21, despite the fact that significantly higher FA-2 concentrations in trisomy 21 and significantly lower concentrations in trisomy 18 had been previously demonstrated in amniotic fluid in the second trimester.     

Age-dependent decrease in embryo implantation rate after in vitro fertilization

OBJECTIVE: To investigate the relation between the implantation rate per embryo after replacement in IVF-ET in relation to female age. DESIGN: Retrospective study using linear and biphasic models in a multivariate analysis. SETTING: Academic tertiary care institution. INTERVENTION(S): In vitro fertilization-ET and determination of gestational sacs at 6 to 7 weeks of pregnancy buy ultrasound. MAIN OUTCOME MEASURE(S): Implantation rate as defined by the number of gestational sacs per embryo replaced. RESULT(S): Woman's age and embryo morphology were strongly related to the implantation rate, indication for IVF-ET and cycle rank number also were related significantly but less strongly. A linear model was built describing the decrease in implantation rate with age, resulting in a decrease of approximately 7%. A biphasic model was tested also and performed significantly better, resulting in a yearly decrease of > 20% after 37 years of age. CONCLUSION(S): The most important independent factors related to the ability of embryos to implant are female age and embryo morphology. The best way to describe the relation with female age is biphasic model with a discontinuity at approximately 37 years of age.     

The pattern of maternal serum inhibin-A concentrations in the second trimester of pregnancy

Maternal serum inhibin-A concentration is a useful marker in prenatal screening for Down syndrome in the second trimester. We measured inhibin-A concentrations in 4304 pregnancies without Down syndrome between 14 and 22 weeks of pregnancy to determine the median values according to gestational age. There was a U-shaped pattern of inhibin-A concentration against gestational age with a minimum concentration at 17 weeks and 1 day (120 days). We suggest that screening centres use a quadratic equation when estimating their normal median inhibin-A level, constraining the shape of the curve and fixing the lower point of the curve to occur at 120 days, but allowing its position in relation to the vertical inhibin-A axis to be set according to the local data. This approach will systematically allow for the changing inhibin-A concentration without introducing the instability of deriving a fresh quadratic equation for each screening centre and each time a centre's medians are revised.     

A preliminary study of parental stress and child behaviour in families with twins conceived by in-vitro fertilization

This paper reports on a preliminary study of parenting quality, parental stress and child behaviour in families with twins conceived by in-vitro fertilization (IVF) in comparison with families with naturally conceived twins. No differences were found between the types of family in parenting quality or child behaviour. However, parents whose children were conceived by IVF reported greater stress associated with parenting than parents with naturally conceived twins.     

Limiting multiple pregnancy in in vitro fertilization/embryo transfer (IVF-ET) cycles

PURPOSE: Our purpose was to assess how the number of embryos transferred can be adjusted to limit multiple gestations. METHODS: A retrospective analysis of 535 consecutive embryo transfers for the years 1991-1993 was conducted. RESULTS: Fewer than three embryos were associated with a low pregnancy rate. Pregnancy rates were highest in women less than 35 when four or more embryos were transferred. With four or more embryos, multiple gestation pregnancy correlated with the number of high-quality embryos transferred. The risk of triplets and quadruplets was greatest for women less than 40. CONCLUSIONS: Multiple-embryo transfer carries a risk of plural gestation. The risk of multiple pregnancy cannot be eliminated without decreasing the pregnancy rate. The risk of high-order multiple pregnancy was best correlated with the number of good-quality embryos transferred. While all are at risk, patients younger than 40 were at highest risk.     

Maternal serum screening for trisomy 18 in the first trimester of pregnancy

It is widely accepted that thrombocytopenia associated with liver cirrhosis is caused by increased platelet destruction in the enlarged spleen, but this issue has not yet been analysed sufficiently in terms of platelet production. Thrombopoietin is produced mainly in the liver and strongly promotes platelet production. We studied serum thrombopoietin and the levels of its mRNA in liver tissue of cirrhotic patients and also in a rat model of liver cirrhosis. Furthermore, to clarify the influence of the spleen, we investigated thrombopoietin mRNA in splenectomized rats. The serum thrombopoietin level in humans with liver cirrhosis was not significantly reduced instead of thrombocytopenia. The expression of thrombopoietin mRNA in liver tissue decreased with the progression of liver cirrhosis in both patients and the rat model and no compensatory expression was observed in other organs or non-parenchymal cells. The level of thrombopoietin mRNA did not differ significantly in splenectomized cirrhotic rats before or after administration of dimethylnitrosamine, but was lower than that in splenectomized rats without cirrhosis. We conclude that thrombocytopenia in liver cirrhosis is caused not only by platelet destruction but also by decreased platelet production, perhaps due to reduction of thrombopoietin mRNA in the liver.