Multi-fetal pregnancy reduction does not influence perinatal results in twin pregnancies.

The objective of this study was to compare perinatal results in multifetal pregnancies where the reduction to twins was performed with non-reduced twin pregnancies. Perinatal results in 99 sets of twins after transabdominal multifetal pregnancy reduction of triple and higher-order multiple pregnancies performed in a single center were compared with a control group consisting of 151 twin pregnancies conceived in the same time period after infertility treatment, which were not a result of reduction. The main outcome measures were length of pregnancies, weight of the newborns, percentage of miscarriages and the mode of the delivery were analyzed. No significant difference could be found at a 5% level of significance regarding the average duration of pregnancy or average weight of the twins. Fisher test on 5% significance level did not ascertain any significant difference in the probability of miscarriage between the group with reduction (5.26%) and the group without reduction (12.84%). At a 5% level of statistical significance, no significant difference in probability of perinatal death of the fetus or delivery of a stillborn fetus was found. The percentage of cesarean sections did not differ significantly in both groups. The analysis of both groups demonstrated that reduction of multifetal pregnancies to twins may not influence perinatal results in comparison to twin pregnancies where reduction was not performed.     

Successful management of quadruplet pregnancy in a perinatal unit.

A case of quadruplet pregnancy is outlined and the management is described to demonstrate the application of monitoring and therapeutic procedures currently available for a multifetal pregnancy. Recording of the nonstressed fetal heart rate, ultrasound monitoring and glucocorticoid stimulation of pulmonary biochemical maturity were done. A successful outcome was achieved with a combined obstetric-neonatal approach and the experience of a perinatal unit.     

Placentation in multiple births.

Outcomes of multifetal pregnancy in prenatal life are markedly affected by chorionicity. Several disease processes are found in monochorionic (MC) twins that do not occur in dichorionic (DC) twins. Improvements in prenatal outcomes will depend on reliable first trimester diagnosis of chorionicity, allowing early monitoring for complications of MC placentation. Particular structures and functions of MC twin placentas affect outcomes and can be targeted for specific treatments, especially in twin-twin transfusion. The causes of severe DC twin fetal growth discordance are clarified. In post-natal life, zygosity is a determining effect in genetic predisposition to many chronic diseases, including neoplasia. Few MC twins know that they are monozygotic (MZ). Few twin researchers realize that MZ twins may be genetically discordant. Abandonment of the word "identical" for MZ twins would assist in clarifying these issues of zygosity, concordance and discordance.     

Prevention of multiple pregnancy during ovulation induction.

Gonadotrophin ovulation induction is currently used for a heterogeneous group of ovulation disorders and unexplained infertility. In the United States it is reported that multiple pregnancy rates of greater than 30% occur as a result of ovulation induction, most commonly after controlled ovarian hyperstimulation and intrauterine insemination. Treatment strategies to reduce the incidence of multiple pregnancies on ovulation induction programs can be targeted to reducing multiple follicular development and subsequent ovulation by a more aggressive cancellation policy, follicle reduction by fine needle aspiration or conversion to IVF; or dealing with the problem of multiple gestation after it has occurred (i.e., multifetal pregnancy reduction). The procedures and abilities exist to resolve this problem. What is needed are appropriate treatment guidelines and well constructed trials to demonstrate that higher order multiple pregnancies can be substantially reduced and/or eliminated without compromising a couple's chances to conceive.     

Routine cervical cerclage in higher order multiple gestation -- does it prolong the pregnancy?

Preterm birth following cervical dilatation is the greatest threat to infants of a multiple pregnancy. Lacking reliable data concerning the effect of prophylactic cerclage, we compared a study group to controls for maternal and perinatal outcome. Sixteen of 94 triplet-, 9 of 18 quadruplet/quintuplet-pregnancies, treated with prophylactic cerclage, were retrospectively compared to those without cervical cerclage respectively. Kruskal-Wallis test and Mann-Whitney-U test were performed as non-parametric one way analysis of variance. For the analysis of frequencies Chi Square test or Fisher's exact test were performed. Odds ratio with 95% confidence interval was used to compare the need for intravenous tocolysis as well as perinatal morbidity and mortality. Gestational age at delivery was not different from the controls in all studied groups. Birth weight revealed a 200 g dominance for the "no cerclage-triplets", while this significant difference was inverted for quadruplets/quintuplets (1245 g vs. 1069 g). With respect to gestational age at birth, need for hospitalisation or medical intervention no benefit was achieved. Moreover, perinatal outcome analysed by arterial pH, APGAR-Score and perinatal mortality was not altered by a prophylactic cerclage. Perinatal morbidity for quadruplets and quintuplets was even higher in cerclage pregnancies. Therefore, these retrospective results disclaim a positive impact of cervical cerclage on pregnancy management or perinatal outcome in multifetal pregnancies.     

Loss in higher multiple pregnancy and multifetal pregnancy reduction.

From early pregnancy into childhood, higher multiples have much higher rates of mortality, whether from spontaneous abortion, the 'vanishing twin' syndrome, fetal or infant death. Many parents must cope with the death of one baby whilst the siblings remain critically ill or later become disabled and yet there grief is often underestimated. Little is known about the long term feelings of parents who choose to have a multifetal pregnancy reduction (MFPR). Most say they made the right decision but also that there was insufficient respect for their loss. They are often anxious about what, if anything, to tell the survivors and how they might react. Long term follow-up studies of the children as well as the parents are needed. Meanwhile parents who chose to have a MFPR must be given more information and ongoing support.     

The context and long-term impacts of multiple birth loss: a peer support network perspective.

Following my own experience with the death of a twin baby, I founded the Center for Loss in Multiple Birth (CLIMB) Inc. During the last 13 years I have worked with nearly 7000 bereaved parents of twins, triplets or other high multiples throughout the US and worldwide. The role of a peer support organisation and the range of families with multiples who have contacted it is described. They come from diverse backgrounds with many forms of bereavement: death during pregnancy, at birth or after of both or all babies, of one twin, of one or more higher order multiples; multifetal pregnancy reduction or selective fetocide; the death of one or more multiples in childhood. Some have had more than one multiple pregnancy and loss. Many are concerned for the surviving children. A peer support organisation has an important role to play in increasing public awareness of the needs of these families as well as influencing policy on infertility treatments that carry a high risk of producing multiple pregnancies with the associated risk of death and disability for one or more of the babies.     

Effect of smoking on circulating angiogenic factors in high risk pregnancies

Objective

Changes in maternal concentrations of the anti-angiogenic factors, soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng), and the pro-angiogenic placental growth factor (PlGF) precede the development of preeclampsia in healthy women. The risk of preeclampsia is reduced in women who smoke during pregnancy. The objective of this study was to investigate whether smoking affects concentrations of angiogenic factors (sFlt1, PlGF, and sEng) in women at high risk for developing preeclampsia.

Study Design

We performed a secondary analysis of serum samples from 993 high-risk women (chronic hypertension, diabetes, multifetal gestation, and previous preeclampsia) in a preeclampsia prevention trial. sFlt1, sEng and PlGF were measured in serum samples obtained at study entry, which was prior to initiation of aspirin (median 19.0 weeks'' [interquartile range of 16.0–22.6 weeks'']). Smoking status was determined by self-report.

Results

sFlt1 was not significantly different in smokers from any high-risk groups compared to their nonsmoking counterparts. PlGF was higher among smokers compared to nonsmokers among diabetic women (142.7 [77.4–337.3] vs 95.9 [48.5–180.7] pg/ml, p = 0.005) and women with a history of preeclampsia (252.2 [137.1–486.0] vs 152.2 [73.6–253.7] pg/ml, p = 0.001). sEng was lower in smokers with multifetal gestations (5.8 [4.6–6.5] vs 6.8 [5.5–8.7] ng/ml, p = 0.002) and trended lower among smokers with diabetes (4.9 [3.8–5.6] vs 5.3 [4.3–6.3] ng/ml, p = 0.05). Smoking was not associated with a lower incidence of preeclampsia in any of these groups.

Conclusions

In certain high-risk groups, smoking is associated with changes in the concentrations of these factors towards a pro-angiogenic direction during early pregnancy; however, there was no apparent association between smoking and the development of preeclampsia in our cohort.     

Hypoganglionosis in pregnancy: a case report

ABSTRACT: INTRODUCTION: We report a very rare case of isolated hypoganglionosis first diagnosed during early pregnancy, which should be discussed from an obstetric and a gastroenterological point of view. CASE PRESENTATION: A pregnant 18-year-old Caucasian woman presented at twelve weeks of gestation with lower abdominal pain, mild constipation and a large abdominal mass. Abdominal and pelvic magnetic resonance imaging demonstrated a megarectum and megasigmoid, and our patient was managed with medical therapy during her pregnancy, which occurred without major incidents. At the onset of labor, a fecaloma obstructing the pelvic outlet was detected, which required manual disimpaction. However, during the procedure a sudden continuous fetal bradycardia was detected. An emergency Cesarean section was performed but the fetus suffered hypoxic ischemic encephalopathy. One year after the delivery, our patient underwent a sigmoid resection. A histopathological analysis revealed a reduction of nerve cells in the myenteric and submucous plexus, suggesting hypoganglionosis. CONCLUSION: Although there are some reports of pregnancies complicated by megacolon, they are too few and too old to delineate guidelines for clinical orientation. In our article, we discuss several issues regarding the management of these rare intestinal innervation disorders during pregnancy that we believe will enhance their obstetric and gastroenterological management during pregnancy.     

The role of ultrasound in multiple pregnancy.

The advances in reproductive technologies have changed the demographics of multifetal pregnancies. In the first trimester, ultrasound allows to diagnose the number of multiples, chorionicity and amnionicity, the presence or absence of nuchal translucency, early growth discordance, severe malformations and the origin of activities and contacts between multiples. In the second and third trimester, the opportunity to examine the cervix by transvaginal ultrasound should not be missed to detect the risk of premature delivery. Ultrasound is essential for the early grading and treatment of twin-to-twin transfusion syndrome (TTTS), the diagnosis of malformations and growth disturbances. Doppler velocimetry has proven to be able to reduce perinatal mortality in twin pregnancies. Finally, ultrasound is used for the detection of the position of multiples and the decision of the optimal route of delivery. This is of main importance in delayed interval delivery and expectant management of multifetal pregnancies and early cervical dilatation.     

Risk of premature birth in multifetal pregnancy.

The risk of preterm delivery (< 37 weeks of gestation) is approximately nine times higher in women with multifetal pregnancies than in women with singleton pregnancies. However, it is possible that the risk will vary according to gestational week. To assess the risk of premature birth within 1 week by gestational age among multifetal pregnancies and compare the estimated risk with that of singleton pregnancies, we analyzed 6,036,475 infants born in singleton pregnancies and 90,887 infants born in multifetal pregnancies in Japan (> or =22 weeks) over the 5-year period 1989-1993. An estimate of the risk of birth within 1 week at gestational week n was obtained by dividing the number of infants delivered at gestational week n by the number of infants delivered at or beyond gestational week n. The risk at 22 weeks was 0.9 per 1000 fetuses for singleton pregnancies and 5.0 per 1000 for multifetal pregnancies. The risk remained relatively stable until 27 weeks of gestation, then sharply increased toward 36 weeks of gestation in both singleton and multifetal pregnancies. The odds ratio for birth within 1 week for fetuses of multifetal pregnancies compared with fetuses of singleton pregnancies was 5.9 (95% CI, 5.4-6.5) at 22 weeks of gestation, increasing gradually with increasing gestational age until 33 weeks of gestation (13.7; 95% CI, 13.1-14.2) but declining thereafter to 8.8 (95% CI, 8.6-8.9) at 36 weeks of gestation. Results of data analysis for each year of the 5-year period did not differ substantially.     

Soluble fms-Like tyrosine kinase 1 (sFlt1), endoglin and placental growth factor (PlGF) in preeclampsia among high risk pregnancies

Background

Differences in circulating concentrations of antiangiogenic factors sFlt1 and soluble endoglin (sEng) and the pro-angiogenic growth factor PlGF are reported to precede the onset of preeclampsia weeks to months in low-risk pregnant women. The objective of this study was to investigate whether similar changes can be detected in pregnant women at high-risk to develop the syndrome.

Methods

This study is a secondary analysis of the NICHD MFMU trial of aspirin to prevent preeclampsia in high-risk pregnancies. Serum samples were available from 194 women with pre-existing diabetes, 313 with chronic hypertension, 234 with multifetal gestation, and 252 with a history of preeclampsia in a previous pregnancy. Samples collected across pregnancy were analyzed in a blinded fashion for sFlt1, sEng and PlGF.

Results

The odds of developing preeclampsia were significantly increased among women with multiple fetuses for each 2-fold elevation in sFlt1, sEng and the ratio of angiogenic factors (e.g. OR 2.18, 95% CI 1.46-3.32), and significantly decreased for each 2-fold elevation in circulating PlGF (OR 0.50, 95% CI 0.30-0.82) between 7 and 26 weeks'' gestation. Cross-sectional analysis of the angiogenic factors across gestation showed significant differences during the third trimester in women who develop preeclampsia compared with appropriate controls in all high-risk groups. However, when data were examined in relation to the gestational week when preeclampsia was diagnosed only sFlt1 was significantly higher 2 to 5 weeks before the clinical onset of preeclampsia and only in women with previous preeclampsia.

Conclusions

The pattern of elevated concentrations of sFlt1 and sEng, and low PlGF in high-risk pregnant subjects who develop preeclampsia is similar to that reported in low-risk pregnant women. However, differences in these factors among high-risk women who do and do not develop preeclampsia are modest, and do not appear to be clinically useful predictors in these high-risk pregnant women.     

Pregnancy Incidence and Risk Factors among Women Participating in Vaginal Microbicide Trials for HIV Prevention: Systematic Review and Meta-Analysis

Introduction

Pregnancy is contraindicated in vaginal microbicide trials for the prevention of HIV infection in women due to the unknown maternal and fetal safety of the microbicides. Women who become pregnant are taken off the microbicide during pregnancy period but this result in reduction of the power of the trials. Strategies to reduce the pregnancy rates require an understanding of the incidence and associated risk factors of pregnancy in microbicide trials. This systematic review estimates the overall incidence rate of pregnancy in microbicide trials and describes the associated risk factors.

Methods

A comprehensive literature search was carried out to identify eligible studies from electronic databases and other sources. Two review authors independently selected studies and extracted relevant data from included studies. Meta-analysis of incidence rates of pregnancy was carried out and risk factors of pregnancy were reported narratively.

Results

Fifteen studies reporting data from 10 microbicide trials (N=27,384 participants) were included. A total of 4,107 participants (15.0%) fell pregnant and a meta-analysis of incidence rates of pregnancy from 8 microbicide trials (N=25,551) yielded an overall incidence rate of 23.37 (95%CI: 17.78 to 28.96) pregnancies per 100 woman-years. However, significant heterogeneity was detected. Hormonal injectable, intra-uterine device (IUD) or implants or sterilization, older age, more years of education and condom use were associated with lower pregnancy. On the other hand, living with a man, history of pregnancy, self and partner desire for future baby, oral contraceptive use, increased number of unprotected sexual acts and inconsistent use of condoms were associated with higher pregnancy.

Conclusions

The incidence rate of pregnancy in microbicide trials is high and strategies for its reduction are urgently required in order to improve the sample size and power of these trials.     

Growth factors in preeclampsia: A vascular disease model. A failed vasodilation and angiogenic challenge from pregnancy onwards?

Preeclampsia is the major cause of maternofetal and neonatal morbi-mortality including intrauterine growth retardation, miscarriages and stillbirths. Inadequate vascular dilation and angiogenesis represent the crucial underlying defect of gravidic hypertension, denoting a failed response to the vasodilatory and pro-angiogenic challenge imposed by pregnancy, especially if multifetal. A similar pathogenesis appears involved in gestational diabetes. In this review we aimed to provide a hint on understanding the deeply involved angiogenic disorders which eventually culminate in utero-placental failure. The key players in these complex processes may be found in an intricate network of growth factors (GFs) and GF inhibitors, controlled by several vascular risk factors modulated by environment and genes, which eventually impact on early and late cardiovascular outcomes of mother and fetus.     

The management and outcome of higher order multifetal pregnancies: obstetric, neonatal and follow-up data.

The objective of this study was to describe current obstetric, neonatal, and long-term neurodevelopmental outcomes of higher order multifetal gestations (> or = 3 fetuses) in the 1990s. We also intended to identify a target gestational age at which neonatal and neurodevelopmental morbidities are low. Records from all multifetal pregnancies (> or = 3 viable fetuses > or = 20 weeks gestation) delivered at the two perinatal centers in Toronto, Ontario, Canada during the study period (January 1, 1990-December 31, 1996) were reviewed. Data were collected on obstetric, neonatal, and long-term neurodevelopmental outcomes. Follow up data were gathered regarding the presence of a severe deficit in four categories (vision, hearing, cognition, and motor skills). Statistical analysis was performed to determine a gestational age at which a significant decrease in deficit occurred. During the study period 165 multifetal pregnancies were delivered. This resulted in 511 fetuses, of which 496 were live births. Of these 496 infants, 453 survived to discharge. Follow up data were obtained on 332 (73.3 per cent) infants. Infant survival increased with gestational age, and was approximately 90 per cent or greater at 26 weeks or more. Of all infants followed, the proportion of those without deficit increased with increasing gestational age, such that the percent without deficit was 96.9 at 31 weeks or greater. Of all infants followed, 301 (90.7 per cent) had no deficit. Statistical analysis revealed a significant difference in long-term neurodevelopmental outcome between infants born before and after 28 weeks gestation. The incidence of a major deficit was 44.1 per cent for those born earlier than and 5.4 per cent for those born later than this gestational age (p = 0.001). In our cohort, survival figures were high. Even in lower gestational groupings, survival was high, but not without serious concerns about severe morbidity. This information is useful when counseling parents of higher order multifetal pregnancies.     

Successful pregnancy in a patient with severe 11-beta-hydroxylase deficiency and novel mutations in CYP11B1 gene

11 beta-Hydroxylase deficiency is a rare form of congenital adrenal hyperplasia, resulting in virilization, glucocorticoid deficiency and hypertension. There have been no previous reports in the literature of a successful pregnancy in a severely affected female. We report the first successful pregnancy resulting in a live birth for a female with 11 beta-hydroxylase deficiency and outline management issues from preconception to successful birth. We also report 2 novel mutations in the CYP11B1 gene leading to 11 beta-hydroxylase deficiency.     

Dichorionic triplets following frozen-thawed poor-stage embryo transfer: a report of two cases and a review

Background

We describe two cases of dichorionic triplet pregnancy after a frozen-thawed poor-stage embryo transfer.

Main body of the abstract

A 39-year-old and a 41-year-old woman underwent ART treatment. The first patient underwent intracytoplasmic sperm injection (ICSI) at 34 years of age, and two frozen-thawed poor-stage embryos were transferred at 39 years of age with assisted hatching, resulting in a trichorionic triamniotic triplet pregnancy. The second patient underwent ICSI, and two poor-grade blastocysts were transferred followed by assisted hatching, resulting in a dichorionic triamniotic triplet pregnancy.In the first case, the heartbeat of one monozygotic twin fetus had stopped on day 48 post-transfer (9 weeks 2 days), resulting in a dichorionic diamniotic twin pregnancy. A healthy boy and girl were delivered by elective caesarean section at 36 weeks, 5-days gestation. In the second case, the patient underwent selective reduction of the monochorionic twins, resulting in a single pregnancy that was vaginally delivered without any problems at 38 weeks 0-days gestation.

Short conclusions

Numerous factors may be associated with the development of a monochorionic pregnancy; however, controversies still remain. The present morphological grading for embryos is insufficient for inhibiting the development of a monochorionic pregnancy.

     

How Do Women Prepare for Pregnancy? Preconception Experiences of Women Attending Antenatal Services and Views of Health Professionals

Main objective

To determine the extent to which women plan and prepare for pregnancy.

Methods

Cross-sectional questionnaire survey of pregnant women attending three maternity services in London about knowledge and uptake of preconception care; including a robust measure of pregnancy planning, and phone interviews with a range of health care professionals.

Main results

We recruited 1173/1288 (90%) women, median age of 32 years. 73% had clearly planned their pregnancy, 24% were ambivalent and only 3% of pregnancies were unplanned. 51% of all women and 63% of those with a planned pregnancy took folic acid before pregnancy. 21% of all women reported smoking and 61% reported drinking alcohol in the 3 months before pregnancy; 48% of smokers and 41% of drinkers reduced or stopped before pregnancy. The 51% of all women who reported advice from a health professional before becoming pregnant were more likely to adopt healthier behaviours before pregnancy [adjusted odds ratios for greatest health professional input compared with none were 2.34 (95% confidence interval 1.54–3.54) for taking folic acid and 2.18 (95% CI 1.42–3.36) for adopting a healthier diet before pregnancy]. Interviews with 20 health professionals indicated low awareness of preconception health issues, missed opportunities and confusion about responsibility for delivery of preconception care.

Significance of the findings

Despite a high level of pregnancy planning, awareness of preconception health among women and health professionals is low, and responsibility for providing preconception care is unclear. However, many women are motivated to adopt healthier behaviours in the preconception period, as indicated by halving of reported smoking rates in this study. The link between health professional input and healthy behaviour change before pregnancy is a new finding that should invigorate strategies to improve awareness and uptake of pre-pregnancy health care, and bring wider benefits for public health.     

A case of left interstitial pregnancy after left adnexectomy--why surgical management?

Interstitial pregnancy is a rare condition of tubal pregnancy with a mortality rate of 2-2.5% [4] that can easily be misdiagnosed. The prevalence of interstitial pregnancy is 0.8% in normal population and it increased during the past few decades due to reproduction techniques development even up to 11% in groups of women after in vitro fertilization. A comprehensive MEDLINE and OLDMEDLINE search covering years 1950-2005 using query terms "interstitial", "pregnancy" and "adnexectomy" identified only 10 cases reported in worldwide literature. The first treatment of interstitial pregnancy used to be a resection of the uterus body via laparotomy. Along with the evolution of sensitive biochemical assays, imaging technologies and the development of operative techniques, the management of interstitial pregnancy became less invasive. We report a case of spontaneous left interstitial pregnancy after left adnexectomy due to left ovarian tumor of borderline malignancy.