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PubMed2004

Elective single-embryo transfer versus double-embryo transfer in in vitro fertilization.

BACKGROUND: The risks of premature birth and perinatal death are increased after in vitro fertilization. These risks are mainly due to the high incidence of multiple births, which relates to the number of embryos transferred. METHODS: We performed a randomized, multicenter trial to assess the equivalence of two approaches to in vitro fertilization with respect to the rates of pregnancy that result in at least one live birth and to compare associated rates of multiple gestation. Women less than 36 years of age who had at least two good-quality embryos were randomly assigned either to undergo transfer of a single fresh embryo and, if there was no live birth, subsequent transfer of a single frozen-and-thawed embryo, or to undergo a single transfer of two fresh embryos. Equivalence was defined as a difference of no more than 10 percentage points in the rates of pregnancy resulting in at least one live birth. RESULTS: Pregnancy resulting in at least one live birth occurred in 142 of 331 women (42.9 percent) in the double-embryo-transfer group as compared with 128 of 330 women (38.8 percent) in the single-embryo-transfer group (difference, 4.1 percentage points; 95 percent confidence interval, -3.4 to 11.6 percentage points); rates of multiple births were 33.1 percent and 0.8 percent, respectively (P<0.001). These results do not demonstrate equivalence of the two approaches in rates of live births, but they do indicate that any reduction in the rate of live births with the transfer of single embryos is unlikely to exceed 11.6 percentage points. CONCLUSIONS: In women under 36 years of age, transferring one fresh embryo and then, if needed, one frozen-and-thawed embryo dramatically reduces the rate of multiple births while achieving a rate of live births that is not substantially lower than the rate that is achievable with a double-embryo transfer.

Adult↗
PubMed1999

Assessment of separate contributions to perinatal mortality of infertility history and treatment: a case-control analysis.

BACKGROUND: Few studies have described the perinatal risks associated with infertility, other than for infertility treated by in-vitro fertilisation or gamete intrafallopian transfer. The aim of this analysis was to estimate the risks of perinatal death associated with treated and untreated infertility. METHODS: A population-based case-control study of perinatal deaths was carried out in Leicestershire Health District over the period 1990-94, during which 60,922 babies were delivered. Of these, 567 perinatal deaths were associated with 542 women. 972 mothers were randomly selected as controls. Medical, obstetric, and social data were collected for cases and controls from the medical notes and interviews with the women. The relative risks of perinatal death associated with treated and untreated infertility before the index pregnancy were estimated as odds ratios by means of unconditional logistic regression analysis. FINDINGS: 65 (10%) of cases and 34 (3.5%) of the controls had infertility before the index pregnancy. History of infertility in the index pregnancy, irrespective of treatment, increased the risk of perinatal death (odds ratio 2.9 [95% CI 1.8-4.5]). The population attributable risk fraction for perinatal death related to infertility was 6.2% (3.4-9.0). 45 (54%) of the deaths, even in the untreated group, were associated with immaturity. Compared with women without infertility, women with untreated infertility were at increased risk of perinatal death (3.3 [1.6-6.8]). The risk of perinatal death associated with multiple births did not explain this finding. Similarly, treated infertility also increased the risk of perinatal death (2.7 [1.5-4.7]); the risks associated with multiple births explained some, but not all, of this excess. In Leicestershire, the overall underlying risk of a mother experiencing at least one perinatal death over the study was 9.0 per 1000 women. For women who experience infertility, this risk increases by about 18 per 1000 (6-30). INTERPRETATION: Counselling for women before any form of infertility treatment should include discussion of the risks of perinatal death. Our results would benefit from confirmation. However, we advocate that at antenatal booking a history of infertility, irrespective of treatment, should be sought, because these women have a significantly increased risk of perinatal death, particularly associated with prematurity.

Adult↗
PubMed1991

Gonadotropin-releasing hormone agonist improves the efficiency of controlled ovarian hyperstimulation/intrauterine insemination.

OBJECTIVE: Leuprolide acetate (LA) has improved the efficiency of human menopausal gonadotropins (hMG) in in vitro fertilization cycles. We hypothesized that the combination of LA/hMG/intrauterine insemination (IUI) would be more efficacious than hMG/IUI cycles. DESIGN: During an 18-month period, all patients completing either a hMG/IUI cycle (group I) or a LA/hMG/IUI cycle (group II) had the characteristics and outcomes of their stimulation cycles assessed. The groups were not prospectively randomized. SETTING: Referral center at a tertiary care hospital. PATIENTS: One hundred twenty three patients in group I completed 219 cycles, and 64 patients in group II completed 102 cycles. Twenty-eight of the patients who failed to conceive with hMG/IUI were advanced to group II. MAIN OUTCOME MEASURES: Pregnancy/IUI is compared between the two groups. RESULTS: Group II demonstrated significantly greater clinical pregnancy/IUI than group I (26.5% and 16.0%, respectively, P less than 0.05), as well as a higher live birth/IUI (21.6% and 12.8%, respectively, P less than 0.05). No difference was present in the rate of fetal wastage or multiple births. CONCLUSIONS: In our patients with recalcitrant infertility, the addition of a gonadotropin-releasing hormone agonist to hMG/IUI improved the pregnancy rate, without increasing the rate of multiple births or fetal wastage.

Female↗
PubMed1993

Iatrogenic multiple pregnancies in East Flanders, Belgium.

OBJECTIVE: To evaluate the specific contribution of artificial induction of ovulation to the increasing number of multiple gestations in East Flanders and the effects of this treatment on the frequencies of monozygotic and dizygotic twinning. DESIGN: Since 1976 the East Flanders Prospective Twin Study has collected data on artificial induction of ovulation for all the multiple births listed in its registry. SETTING: East Flanders Prospective Twin Survey. PATIENTS: Between 1976 and 1992, 458 twin and 78 triplet pregnancies resulting from artificial induction of ovulation were analyzed. MAIN OUTCOME MEASURES: Zygosity and frequency of iatrogenic multiple births. RESULTS: Since 1985 there is an explosive increase in twin and triplet births in East Flanders. This increase has been caused mainly by the sole use of fertility-enhancing drugs and in the last few years by resorting to other technologies of assisted reproduction, such as IVF-ET, GIFT, or zygote intrafallopian transfer. CONCLUSION: In view of the elevated risk inherent to multiple pregnancies in terms of perinatal mortality and morbidity, the over enthusiastic or improper use of fertility drugs should be curtailed.

Belgium↗
PubMed2006

Policy efforts to prevent ART-related preterm birth.

At 12.5%, the preterm birth rate is the highest it has ever been in the US. In tandem with the rise in preterm birth is a dramatic increase in multiple birth rates. The recent trend of delayed maternal age at first birth and the associated use of assisted reproductive technologies (ARTs) have led to the increase in multiple gestation and its attendant increased risk for preterm birth. While ARTs are not responsible for the majority of preterm births, the attributable fraction has increased, is iatrogenic- and preventable. Despite widespread recognition of this problem, the rate of associated twin gestation has not decreased. We offer options for policymakers on several levels--from medical to health systems to societal policy--to decrease ART-related preterm births.

Embryo Transfer↗
PubMed1988

Cigarette smoking as risk factor for late fetal and early neonatal death.

Risk factors for late fetal death and early neonatal mortality were examined in a population based prospective study. Practically all Swedish births between 1983 and 1985 were included, 281,808 births in all. The overall rates of late fetal death and early neonatal mortality were 3.5 and 3.1 per 1000, respectively. About 30% of the pregnant women were recorded as being daily smokers. Logistic regression analyses showed significant relative risks for late fetal death for high maternal age (1.4), nulliparity (1.4), multiparity (greater than or equal to 2) (1.3), smoking (1.4), and multiple births (2.8). Significant relative risks for early neonatal mortality were found for multiple births (4.9) and smoking (1.2). Smokers aged under 35 faced a relative risk of late fetal death ranging from 1.1 to 1.6, while the risk for late fetal death was doubled if the mothers were aged 35 years or more and smoked. In countries like Sweden, where maternal cigarette smoking is prevalent, smoking may be the most important preventable risk factor for late fetal death.

Female↗
PubMed1995

[Pregnancy, births and infants after in-vitro-fertilization in Norway, 1988-1991].

We studied 1,165 pregnancies after in vitro fertilization in six public hospitals in Norway in the years 1988-91. The annual number of pregnancies increased from 158 in 1988 to 365 in 1991. The mean number of replaced embryos was reduced from 3.7 to 2.7. The rate of multiple births was not significantly altered in the same period, 24.3% were twin births and 5.7% triplet births. 19.3% of the pregnancies ended in abortion and 8.4% were ectopic. 782 births were registered in the Medical Birth Registry of Norway and compared with all other births during the period. Gestational hypertension, bleeding and preterm birth were observed more often in pregnancies after in vitro fertilization. The proportion of infants with very low birth weight (> 1,500 g) after in vitro fertilization was 9.7%, and nearly 50% of these were triplets. The relative risk of stillbirth and death during the first year of life, adjusted for maternal age and birth order, was 3.1 (95% CI 2.4-4.0) and 2.3 (95% CI 1.5-3.5) for singletons alone. The proportion of multiple births should be reduced.

Female↗
PubMed2003

Neonatal lenticulostriate vasculopathy: further characterisation.

BACKGROUND: Lenticulostriate vasculopathy (LSV) is sometimes detected on routine brain ultrasonography in neonates, and is often associated with various perinatal and neonatal abnormalities. However, most reports on LSV are retrospective with no controls. OBJECTIVES: To compare the perinatal and neonatal clinical characteristics of neonates with LSV with matched controls and to summarise all published reports of LSV. DESIGN: A prospective study that summarises the clinical, laboratory, and neurosonographic data of neonates with LSV. METHODS: Of 1184 neonates admitted to the neonatal intensive care unit (NICU) during a three year period, 857 had a routine head ultrasound examination. Twenty one had LSV, and were compared with 42 matched controls with regard to gestational, perinatal, neonatal, laboratory, and neurosonographic characteristics. RESULTS: LSV was detected in 21 of the 857 (2.45%) neonates. It was bilateral in 10 of the 21 cases and located in the thalamus (n = 14) and basal ganglia (n = 7). Infants with LSV were not significantly different from matched controls in most tested variables. However, compared with the control group, the LSV group included significantly more multiple births and more disturbances in amniotic fluid volume, but less meconial amniotic fluid. In addition, the patients with LSV required fewer blood transfusions and less phototherapy. CONCLUSIONS: Except for more multiple births, neonates with LSV did not display more adverse findings than their matched controls.

Basal Ganglia Cerebrovascular Disease↗
PubMed2002

The occurrence of chronic disease and other conditions in a large population-based cohort of native Californian twins.

We describe the prevalence of chronic diseases and conditions in a large cohort of twins, which has been developed to facilitate studies of the role of genetics and environment in the development of disease. The California Twin Program (CTP) comprises twins born in California between 1908 and 1982. Birth records from all multiple births (256,616 in total) were linked (multiple times between 1990 and 2001) with the California Department of Motor Vehicles (DMV) roster of licensees to obtain address information. The linkages have revealed 161,109 matches and, because of less complete DMV records in some years, were less successful in older females than in all others. To date over 51,000 of these twins have completed a detailed 16-page mailed risk factor questionnaire. Based on estimates of numbers of individuals receiving a questionnaire, our crude response rates are as high as 63.6% (among females currently in their 50s), with an overall crude response rate of 37.9%. Similar to our previous report regarding the first 42,000 twins, the current group who have completed the questionnaire are representative of the population from which they were drawn (in terms of age, sex, race and residential distribution). Self-reported disease frequencies are provided, along with current estimates of future cancer incidence and mortality rates likely to be observed in the group. We outline our plans for cohort expansion, additional studies using the cohort, and future plans for inviting collaboration.

Adolescent↗
PubMed1992

A registry study of very low birthweight liveborn infants in Sweden, 1973-1988.

Very low birthweight liveborn infants (less than 1,500 g, VLBW) born in Sweden 1973-88 were identified from the Medical Birth Registry and efforts were made to remove wrongly recorded birthweights--9% of infants with a registered birth weight below 1,500 g were removed. Some VLBW infants were not recorded in the register and the estimate of the prevalence at birth of VLBW infants is therefore slightly underestimated. It increased from about 5.5 per 1,000 during the period 1973-84 to 6.7 per 1,000 during 1987-88. 18% of VLBW infants were involved in multiple births. Median Apgar score at 5 min increased for each 100 g birthweight class. Even at a birthweight between 1,400 and 1,499 g, a low Apgar score at 5 min was seen in 20%. The rate of cesarean section increased between 1973 and 1983 from about 10% to 60%. One-year survival for infants with a birthweight less than 1,000 g increased from less than 20% in 1973-75 to 50% in the 1986-88 cohorts. Corresponding figures for infants with a birthweight between 1,000 and 1,499 g were 60% and 90%. A markedly better one-year survival is already evident in the 600-699 g class. On stratifying for 100 g birthweight class, perinatal death risk was higher in boys than in girls and higher in multiple births than in singletons. An increased rate of congenital malformations was seen in the 1,000-1,499 g class but not in the less than 1,000 g class.

Apgar Score↗
PubMed2004

[Management of twin births].

INTRODUCTION: The rate of multiple births has increased all over the world in the past decade. This is mainly due to the widespread use of infertility treatments and assisted reproductive techniques. Despite of improvements in obstetric and neonatal care, twin pregnancy still mean high risk both for the mothers and their babies. The management of twin delivery remains controversial. PATIENTS AND METHOD: Authors analyzed the data of all twin pregnancies at the Department of Obstetrics and Gynecology, University of Debrecen between January 2002 and December 2003. The data of 113 twin pregnancies were analyzed. Details of gestational age, presentation, birth weight discordance, mode of delivery were reviewed. RESULTS: From the 113 analyzed twin births, 27 pregnancies have been conceived after successful assisted reproductive technique. In 18 cases more than 500 grams of body weight difference was detected between the two babies at the time of delivery. The rate of preterm birth was 69%, and cesarean section was performed in 64% of preterm births compared to 68.6% in the matured delivery group. CONCLUSIONS: On the basis of recent data a large prospective, randomized trial is mandatory to determine the optimal management of twin deliveries.

Cesarean Section↗
PubMed1982

Sib risks for nonspecific mental retardation in British Columbia.

Cases of nonspecific mental retardation (MR) born in British Columbia between 1952 and 1970 ascertained through the British Columbia Health Surveillance Registry were linked by birth registration number to family sibships from computer-linked groupings of birth and marriage records in British Columbia. It was possible to retrieve family information for 97% of the cases by this method. Because of good ascertainment and relatively large sample size, the 1952-1965 birth cohort comprising 2,209 index cases was selected for calculations of overall risks and recurrence risks to sibs categorized by sex, MR level, associated neurological disability, and singleton versus multiple birth. The overall risk of affected individuals among all sibs was 4.4 +/- 0.6%, which was about ten times greater than the minimum population incidence of nonspecific MR. The risk among subsequent sibs of the first affected case in a family was 3.7 +/- 0.8%. These risks varied depending on sex, MR level, and whether the mental retardation was associated with hydrocephalus, microcephalus, cerebral palsy, or epilepsy. The recurrence risk after two affected individuals was 12 +/- 7%--about three times greater than after one affected individual. Even though the frequency of MR is greater among twins than in the overall population, the recurrence risk of nonspecific MR was not significantly different for index cases from either singleton or multiple births.

British Columbia↗
PubMed2001

Long-term impact of reproductive factors on the risk of cervical, endometrial, ovarian and breast cancer.

The influence of maternal age, parity, low or high birthweight, multiple births, and pre-eclampsia on the risk of cervical, endometrial, ovarian and breast cancers was studied. Data on 40951 women and the outcomes of their deliveries between 1955 and 1995 were obtained from birth registers. For the mothers, data from the Swedish Cancer Registry and the Cause of Death Register were added. The sample was evaluated using Cox's regression in univariate and bivariate analyses where the relative risk and its 95% confidence interval were calculated. Increasing maternal age at first birth was associated with an increasing relative risk of endometrial, ovarian, and breast cancers, and with a decreased risk of cervical cancer. Multiparity was a protective factor for all gynaecological cancers, including cervical and breast cancers. Multiple births were associated with an increased risk of endometrial cancer.

Adolescent↗
PubMed1990

"Twins in school". An Australia-wide program.

The multiple birth family is more likely to have a dispute with the education system than with any other service. So many potential areas of conflict exist over the abilities and behaviour of multiples and over such issues as separation or keeping back one twin. One reason for disputes is the lack of good data to adequately reflect the different perspectives of parents and teachers and the differing needs of families: the same solution does not apply to all. To provide the first large-scale data base and building upon an initial survey of 85% of all primary school teachers in South Australia, the LaTrobe Twin Study and AMBA worked with Education Departments to set-up in each state Education Research Teams (ERTs) of parents of multiples who were also teachers. The ERTs were crucial in three phases. 1) Developing and circulating questionnaires and publicising the nationwide survey. 784 families and 1264 teachers of their children completed these questionnaires, many reporting that simply having to address the issues raised in the questionnaire was a valuable learning experience. 2) Exploring the data base. Issues arising included the very different bases on which parents and teachers judged separation desirable, with teachers emphasising the unsubstantiated claim that separation is essential to individual development. Separation became more common over the first three years of schooling but 20-25% of twins separated one year were back together the next. 3) Running regional meetings of parents, teachers and administrators to discuss the results and to pool experiences and plan policies at the local level. A need clearly exists to improve the level of consultation between families and school personnel and to ensure the widespread availability of information which identifies key issues in making decisions for that multiple birth family.

Anxiety, Separation↗
PubMed2003

Populations at risk for developing respiratory syncytial virus and risk factors for respiratory syncytial virus severity: infants with predisposing conditions.

According to National Vital Statistics Reports, premature infants (< 36 weeks gestation) account for approximately 7.4% of all births. During the 8 years from 1989 to 1997, multiple births steadily increased across all categories from twin to quintuplet and higher orders. During that same period low birth weight (< 2500 g) births increased almost 12%, and very low birth weight (< 1500 g) births increased approximately 20%.Attendant to these national trends in multiple and preterm births, overall gestation-specific survival rates have improved substantially. This improved outcome can be attributed in large measure to advances in neonatal care and technology. Despite the encouraging statistics on survival, infants born prematurely, at low or very low birth weights and/or with chronic conditions that predispose to lower respiratory tract illness, continue to incur serious risk of long term morbidity and the consumption of inpatient hospital services. In a recent 2-year study of US children, low and very low birth weights were found to be independent risk factors for bronchiolitis-associated mortality. In the past 14 years what defines bronchopulmonary dysplasia (BPD)/chronic lung disease (CLD) has shifted away from clinical, radiographic and pathologic findings in the preterm infant toward the pathophysiology of arrested lung development and the need for supportive care beyond 36 weeks corrected gestational age. The incidence of BPD/CLD ranges from 14 to 43%, with higher rates observed among infants of lower gestational age and birth weight. The health care team approach to the management of BPD directs its efforts toward minimizing pulmonary vascular resistance, alleviating airway obstruction and improving short term lung mechanics. Measures to prevent BPD/CLD attempt to forestall both acute and chronic lung function abnormalities. To that end researchers have investigated the early use of continuous positive airway pressure, vitamin supplementation and recombinant human copper/zinc superoxide dismutase. Despite significant gains in the survival of infants born at lower gestational ages, prematurity, low birth weight and/or underlying chronic pulmonary disease put the pediatric patient at risk for increased frequency and severity of respiratory syncytial virus lower respiratory tract illness and the potential for its long term sequelae.

Airway Obstruction↗
PubMed2000

Microsurgical vasovasostomy versus microsurgical epididymal sperm aspiration/testicular extraction of sperm combined with intracytoplasmic sperm injection. A cost-benefit analysis.

PURPOSE: Vasovasostomy (VVS) represents the standard therapy of choice for the treatment of obstructive azoospermia following vasectomy. However, recently, intracytoplasmic sperm injection (ICSI) has been suggested by some to represent the solution for all cases of malefactor infertility regardless of its etiology based on its success rates. Therefore, we compared VVS to microsurgical epididymal sperm aspiration (MESA)/testicular extraction of sperm (TESE) and ICSI in terms of pregnancy, complications, and costs. PATIENTS AND METHODS: Between 1/93 and 6/98, 157 VVS were performed microsurgically using the double-layer technique. Between 9/94 and 9/97, 69 and 42 couples underwent MESA/ICSI and TESE/ICSI, respectively, for epididymal obstruction and azoospermia of testicular origin. RESULTS: The mean interval of vasal obstruction was 7.6 (0.5-18) years; patency after VVS was 77%, pregnancy rate was 52%. Local complication rate was 4.7%, no major complications were observed. Costs per life birth after VVS were 5,447 DM or 2,793 Euro. Pregnancy rates after MESA/TESE and ICSI were 22.5 and 19.5%, respectively, with 16 singletons, 3 twins and 3 abortions; local complications occurred in 3.9% of the men. Multiple births were noticed in 15.8% following ICSI, but in only 0.7% following VVS. 5.7 and 1.4% of the female partners experienced serious complications (mild or severe ovarian hyperstimulation syndrome, respectively). Costs per life birth after a MESA/TESE cycle amounted to 28,804 DM or 14,547 Euro. CONCLUSIONS: Even in the era of ICSI, microsurgical VVS represents the standard approach for obstructive azoospermia following vasectomy. Based on a cost-benefit analysis, VVS is more successful in terms of pregnancy rates (52 vs. 22.5%). VVS does not expose the female partners to complications following treatment of male infertility. In contrast to ICSI, multiple birth rates do not increase after VVS. We conclude that MESA/ICSI should be reversed for patients who are not amenable for microsurgical reconstruction.

Adult↗
PubMed2002

The East Flanders Prospective Twin Survey (EFPTS).

The East Flanders Prospective Twin Survey (EFPTS) is a registry of multiple births in the province of East-Flanders, Belgium. It has several unique features: it is population-based and prospective, with the possibility of long-term follow-up; the twins (and higher order multiple births) are ascertained at birth; basic perinatal data are recorded; chorion type and zygosity are established; and since 1969 placental biopsies have been taken and frozen at -20 degrees C for later determination of genetic markers. The EFPTS is the only large register that includes placental data and allows differentiation of three subtypes of monozygotic (MZ) twins based on the time of the initial zygotic division: the dichorionic-diamnionic pairs (early, before the fourth day after fertilisation), the monochorionic-diamnionic pairs (intermediate, between the fourth and the seventh day post fertilisation), and the monochorionic-monoamnionic pairs (late, after the eight day post fertilisation). This added a new dimension to didymology (the science of twins; delta iota delta upsilon mu omicron zeta = twins): the timing of twinning. Studies can be initiated on primary biases, those originating "in utero". Such studies may throw new light on the controversy over the validity of the classic twin method, the consequences of early embryological events (before and just after implantation of the embryo), the origin of congenital malformations, the sex proportion of multiples, the gene-environment interactions as far as intrauterine environment is concerned, to name but a few.

Belgium↗