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Biomedical subjects

D M Saunders

Publications and source records attributed to D M Saunders.

At least 19 recordsLinked to original sources

Children conceived using ICSI do not have an increased risk of delayed mental development at 5 years of age.

BACKGROUND: Concerns about possible adverse outcomes for children conceived using ICSI were highlighted in 1998 when 1-year-old ICSI children were found to be at increased risk (relative risk = 9.2) of delayed mental development compared with children conceived naturally or using IVF. As the findings were biologically plausible, it was considered important to reassess child development when a more accurate measure of long-term cognitive ability could be obtained. METHODS: The mental development of 97 ICSI, 80 IVF and 110 naturally conceived (NC) children at 5 years of age was assessed using intelligence quotients (IQ) obtained from the Wechsler Preschool and Primary Scales of Intelligence. RESULTS: The mean full-scale IQ was 110 +/- 18 for ICSI, 111 +/- 13 for IVF and 114 +/- 13 for NC children (P = 0.21, non-significant). ICSI children were not at increased risk for delayed (full-scale IQ <85) cognitive development (ICSI 5.2%, IVF 2.5%, NC 0.9%; P = 0.18, non-significant). The only significant independent predictor of below-average full-scale IQ on multivariate analysis was lower maternal education level. CONCLUSIONS: These findings suggest that the genetic influence of parental cognitive ability is more important than the mode of conception in determining the long-term intellectual ability of children conceived using ICSI.

Case-Control Studies↗

Parental adjustment and attitudes to parenting after in vitro fertilization.

OBJECTIVE: To examine the psychosocial and parenthood-specific adjustment and attitudes to parenting at 1 year postpartum of IVF parents. DESIGN: Prospective, controlled study. SETTING: Volunteers in a teaching hospital environment. PATIENT(S): Sixty-five primiparous women with singleton IVF pregnancies and their partners, and a control group of 61 similarly aged primiparous women with no history of infertility and their partners. INTERVENTION(S): Completion of questionnaires and interviews. MAIN OUTCOME MEASURE(S): Parent reports of general and parenthood-specific adjustment and attitudes to parenting. RESULT(S): The IVF mothers tended to report lower self-esteem and less parenting competence than control mothers. Although there were no group differences on protectiveness, IVF mothers saw their children as significantly more vulnerable and "special" compared with controls. The IVF fathers reported significantly lower self-esteem and marital satisfaction, although not less competence in parenting. Both IVF mothers and fathers did not differ from control parents on other measures of general adjustment (mood) or those more specific to parenthood (e.g., attachment to the child and attitudes to child rearing). CONCLUSION(S): The IVF parents' adjustment to parenthood is similar to naturally conceiving comparison families. Nonetheless, there are minor IVF differences that reflect heightened child-focused concern and less confidence in parenting for mothers, less satisfaction with the marriage for the fathers, and vulnerable self-esteem for both parents.

Attitude↗

The mother-child relationship following in vitro fertilisation (IVF): infant attachment, responsivity, and maternal sensitivity.

Infant attachment and mother-child interaction were evaluated for 65 primiparous women and their singleton infants conceived through in vitro fertilisation (IVF) and a control group of 61 women and their infants conceived naturally. The sample was enrolled during pregnancy as part of a longitudinal study. At 12 months postpartum, security of infant attachment was assessed using the Strange Situation procedure, and mother-child interaction was assessed in a free play context using the Emotional Availability Scales. IVF children demonstrated predominantly secure attachment relationships with their mothers (64.6% IVF, 55.9% controls), and there were no significant between-group differences in the proportion of IVF compared to control group children classified in any of the secure or insecure attachment groups. Furthermore, there were no significant group differences on maternal (sensitivity, structuring, hostility) or child (responsivity, involving) dimensions of interaction during play. The majority of IVF mothers (86%) were sensitive and their infants responsive (91%). Contrary to expectation, mother's ratings of greater anticipated infant difficultness assessed during pregnancy and higher ratings of infant temperament and behaviour difficulty assessed at 4 and 12 months postpartum were associated with secure attachment relationships and more optimal mother-child interaction in both the IVF and control groups.

Adult↗

Medical and developmental outcome at 1 year for children conceived by intracytoplasmic sperm injection.

BACKGROUND: Intracytoplasmic sperm injection (ICSI) was introduced as a new form of in-vitro fertilisation (IVF) in 1993 and is now accepted as the treatment of choice for severe male infertility in many centres around the world. However, there is little information about the long-term outcome of children conceived by ICSI. We aimed to find out the medical and developmental outcome of children conceived by ICSI at age 1 year. METHODS: In this prospective study, we compared the medical and developmental outcome at 1 year of 89 children conceived by ICSI with 84 children conceived by routine IVF, and with 80 children conceived naturally. Formal developmental assessment was done with Bayley Scales of Infant Development (2nd edition) from which a mental development index (MDI) was derived. FINDINGS: There was no significant difference in the incidence of major congenital malformations or major health problems in the first year of life. However, the mean Bayley MDI was significantly lower for the children conceived by ICSI than for the children conceived by routine IVF or naturally (95.9 [SD 10.7], 101.8 [8.5], and 102.5 [7.6], respectively, p < 0.0001). 15 (17%) of 89 children conceived by ICSI experienced mildly or significantly delayed development (MDI < 85) at 1 year compared with two (2%) of the 84 children conceived by IVF and one (1%) of the 80 children conceived by natural conception (p < 0.0001). INTERPRETATION: Although most children conceived by ICSI are healthy and develop normally, there is an increased risk of mild delays in development at 1 year when compared with children conceived by routine IVF or conceived naturally. These findings support the need for ongoing developmental follow-up of children conceived by ICSI to see whether they are at increased risk of intellectual impairment or learning difficulties at school age.

Adult↗

Development, behaviour and temperament: a prospective study of infants conceived through in-vitro fertilization.

The development, behaviour and temperament of 65 singleton infants conceived through in-vitro fertilization (IVF) and 63 matched controls were compared at 1 year postpartum. Primiparous women were recruited during pregnancy and their infants' development was assessed at 1 year. In addition, test-taking behaviour was evaluated by an examiner using the Bayley behaviour rating scale and mothers completed a behaviour problem checklist and temperament scale. Mental, motor, speech and social development were appropriate for age, with no significant group differences. While receptive language development was in the normal range, IVF infants scored lower than control infants. Across both groups, mothers reported low levels of behaviour difficulty and mean temperament ratings were in the general population range. There were no group differences in observed test-taking behaviour. However, IVF mothers rated their children at a higher level of behaviour difficulty and more reactive than the ratings given by control mothers. Overall, singleton children conceived through IVF demonstrate appropriate general development at 1 year of age. The higher reported behaviour difficulty experienced by IVF mothers may reflect their concerns about the well-being and adjustment of their child during the first year.

Adult↗

Infants conceived using in-vitro fertilization do not over-utilize health care resources after the neonatal period.

Health outcomes during the first year for 95 infants born following in-vitro fertilization (IVF) were compared with those of 79 naturally conceived controls whose mothers were of identical parity and similar age. Primigravid women were enrolled prospectively at 30 weeks gestation, perinatal and neonatal data were collected during pregnancy and following birth, and details of health care resource use were obtained from mothers at 4 and 12 months. Median (range) number of medical problems during the first year tended to be less for IVF infants, 4 (0-41) versus 5 (0-12) (P = 0.07), whilst total number of visits to health care workers was similar for IVF and control infants, 19 (2-47) versus 19 (1-47). IVF infants were more likely to have an excessive number of visits to Early Childhood Health Care Centres [odds ratio (OR; 95% confidence interval, CI) = 2.44 (1.11-5.56)], but less likely to have an excessive number of visits to general medical practitioners [OR = 0.45 (0.22-0.93)] and other health care workers [OR = 0.48 (0.23-0.99)]. These data provide some degree of reassurance about medium-term health outcomes for children conceived using IVF. Although they are more likely to utilize the resources of neonatal intensive care units, IVF infants do not appear to have an increased number of medical problems or to over-utilize health care resources during the remainder of their first year of life.

Adult↗

Serum from women with preeclampsia partially corrects the abnormal in vitro prostacyclin secretion of preeclamptic villous cytotrophoblasts but not that of prostaglandin E2 or endothelin-1.

OBJECTIVE: This study was conducted (1) to determine in vitro placental villous cytotrophoblast secretion of prostacyclin, prostaglandin E2, and endothelin-1, (2) to examine the effect of serum from normal and preeclamptic women on secretion of these vasoactive substances, and (3) to determine whether responses to these sera by cytotrophoblasts from preeclamptic pregnancies are different from those of normal pregnancies. STUDY DESIGN: Cytotrophoblasts isolated from human placentas collected at cesarean section from normal and preeclamptic women were incubated for 20 hours in 20% (vol/vol) sera from preeclamptic or gestational age-matched normal pregnant women. Levels of prostacyclin (measured as 6-keto-prostaglandin F1alpha), prostaglandin E2, and endothelin-1 were measured in cytotrophoblast supernatants. RESULTS: In normal pregnancy sera preeclamptic cytotrophoblasts secreted significantly lower amounts of prostacyclin and prostaglandin E2 but higher amounts of endothelin-1 than did normal cytotrophoblasts. In preeclamptic sera the abnormality of prostacyclin secretion by preeclamptic cytotrophoblasts was partially corrected, but there was no effect on prostaglandin E2 or endothelin-1 secretion. Preeclamptic sera had no effect on secretion by normal cytotrophoblasts. CONCLUSIONS: The differences between normal and preeclamptic cytotrophoblasts in prostacyclin, PGE2, and endothelin-1 secretion and in response to preeclamptic serum suggest altered arachidonic acid metabolism in preeclampsia.

Blood Physiological Phenomena↗

Trophoblast antigen levels in the first trimester of a trisomy 22 pregnancy.

We report trophoblast antigen (pregnancy-associated plasma protein-A, PAPP-A; free beta-human chorionic gonadotrophin, F beta hCG) expression in a trimosy 22 pregnancy. Maternal concentrations of these antigens were depressed prior to detection of abnormalities by ultrasonography. Immunohistochemical findings were consistent with depressed marker expression.

Chorionic Gonadotropin, beta Subunit, Human↗

In-vitro secretion of prostanoids by placental villous cytotrophoblasts in pre-eclampsia.

Villous trophoblasts isolated from term placentae of normal pregnancies, and pregnancies complicated by chronic hypertension or pre-eclampsia, were examined over 7 days in primary culture. Low levels of prostaglandin E2 and prostacyclin (measured as 6-keto prostaglandin Fl alpha) were secreted by trophoblast cells from all three clinical groups. Secretion was maximal at day 1 and decreased exponentially thereafter. Thromboxane secretion also fell sequentially from day 1. Thromboxane secretion by pre-eclamptic trophoblasts was three to four times that of cells from normal or chronically hypertensive subjects. Prostanoid secretion by isolated cultured cytotrophoblasts was not dependent on aggregation or morphological alteration, nor related to changes in progesterone or human chorionic gonadotrophin production. Because the local maternal circulation is exposed to substances secreted by this cell population, thromboxane could be the trigger for vasoconstriction and coagulation found within the maternal uteroplacental circulation in pre-eclampsia.

6-Ketoprostaglandin F1 alpha↗

Triple test for prenatal detection of Edwards syndrome (trisomy 18).

OBJECTIVE(S): To demonstrate the limitation of complete reliance on computer generated interpretations and to highlight the need for understanding of pregnancy-related biochemistry when offering prenatal screening. METHODS: Four cases of cytogenetically confirmed trisomy 18 pregnancies are presented. All four cases underwent prenatal screening (Triple Test-AFP, uE3, t beta-hCG) at midgestation and risk assessment by the alpha algorithm. RESULTS: All four cases of trisomy 18 were assessed as being at low risk for DS and/or open NTD. Although marker levels were not consistent with either of these clinical situations, they were indicative of a compromised pregnancy. Circulating levels of trophoblast-derived antigens (uE3, t beta-hCG) were depressed (< or = 0.5 MoM) in all four cases. Further investigations (ultrasonography, amniocentesis) confirmed a trisomy 18 fetus. CONCLUSIONS: Risk assessment by computer based algorithms relies on maternal factors and specific DS/NTD marker profiles. Aberrant marker profiles are not distinguished from normal. Therefore, it is essential that prenatal screening is offered only by those competent in pregnancy biochemistry and able to identify these abnormal situations.

Adult↗

Clinical intracytoplasmic sperm injection (ICSI) results from Royal North Shore Hospital.

The technique of intracytoplasmic sperm injection (ICSI) was first introduced to the Royal North Shore Hospital in April 1993 as part of a controlled study of 100 patient cycles in which sibling oocytes were inseminated by either subzonal insemination (SUZI) or ICSI. This trial showed direct sperm injection to be superior in terms of fertilization. In that study, 58 embryo transfers of 101 ICSI-derived embryos resulted in 10 pregnancies. No miscarriages have occurred and a total of 10 fetal hearts (9.8% per embryo transferred) were detected on ultrasound. There have been 10 deliveries of 10 babies. Since the beginning of 1994, intracytoplasmic injection has been used exclusively for patients requiring micromanipulation to achieve fertilization. There have been 200 patient cycles with 1650 oocytes collected (8.8 oocytes per cycle). Of these oocytes, 1548 were mature (94%) and were subjected to ICSI, and normal fertilization occurred in 874 (56%) of the injected oocytes. The number of oocytes which cleaved and were suitable for fresh transfer or cryopreservation was 818 (94%). There have been 153 fresh embryo transfers of 326 embryos. Twenty-six pregnancies (17% per embryo transfer) have resulted, 22 of which proceeded to ultrasound examination in which 23 fetal hearts were detected (7% per embryo transferred). Three miscarriages have occurred, leaving 19 ongoing pregnancies. There have been 127 cryopreservation procedures involving 492 embryos. To date, there have been 47 embryo thaw cycles, and 93 of the 115 (81%) thawed embryos survived and were transferred. These 47 embryo transfers resulted in 10 pregnancies (21% per embryo transfer), one of which one has miscarried.(ABSTRACT TRUNCATED AT 250 WORDS)

Australia↗