Alice M. Jaques

Prevalence and risk factors for obstetric haemorrhage in 6730 singleton births after assisted reproductive technology in Victoria Australia

BACKGROUND Obstetric haemorrhages have been reported to be increased after assisted reproduction technologies (ART) but the mechanisms involved are unclear. METHODS This retrospective cohort study compared the prevalence of antepartum haemorrhage (APH), placenta praevia (PP), placental abruption (PA) and primary post-partum haemorrhage (PPH) in women with singleton births between 1991 and 2004 in Victoria Australia: 6730 after IVF/ICSI, 24 619 from the general population, 779 after gamete intrafallopian transfer (GIFT) and 2167 non-ART conceptions in infertile patients. Risk factors for haemorrhages in the IVF/ICSI group were examined by logistic regression. RESULTS The IVF/ICSI group had more APH: 6.7 versus 3.6% (adjusted OR 2.0; 95% CI 1.8-2.3), PP: 2.6 versus 1.1% (2.3; 1.9-2.9), PA: 0.9 versus 0.4% (2.1; 1.4-3.0) and PPH: 11.1 versus 7.9% (1.3; 1.2-1.4) than the general population. APH, PP and PA were as frequent in the GIFT group as in the IVF/ICSI group, but were less frequent in the non-ART group. Within the IVF/ICSI group, fresh compared with frozen thawed embryo transfers (FET) was associated with more frequent APH (1.5; 1.2-1.8) and PA (2.1; 1.2-3.7) and the odds ratio increased with number of oocytes collected (1.02; 1.00-1.04). Endometriosis patients had more PP (1.7; 1.2-2.4) and PPH (1.3; 1.1-1.6) than those without endometriosis. FET in artificial cycles was associated with increased PPH (1.8; 1.3-2.6) compared with FET in natural cycles. CONCLUSIONS Obstetric haemorrhages are more frequent with singleton births after IVF, ICSI and GIFT. The exploratory analysis of factors in the IVF/ICSI group, showing associations with fresh embryo transfers in stimulated cycles, endometriosis and hormone treatments, suggests that events around the time of implantation may be responsible and that suboptimal endometrial function is the critical mechanism.

Preterm birth, ovarian endometriomata, and assisted reproduction technologies

OBJECTIVE To report preterm birth and small for gestational age (SGA) rates from assisted reproduction technologies (ART) patients with ovarian endometriomata compared with control groups. DESIGN Retrospective cohort study. SETTING Tertiary university affiliated ART center and Perinatal Data Collection Unit (PDCU). PATIENT(S) Every woman who had an ART singleton baby born between 1991 and 2004 had her database record assessed (N = 4382). Control groups included 1201 singleton babies from ART patients without endometriosis and 2400 randomly selected women from the PDCU database of 850,000 births. INTERVENTION(S) There were 95 singleton ART babies from patients with ovarian endometriomata and 535 ART singleton babies from patients who had endometriosis but no ovarian endometriomata. MAIN OUTCOME MEASURE(S) Preterm birth rates and SGA birth rates. RESULT(S) Preterm birth rate increased only in the ovarian endometriomata group when compared with community birth records (n = 850,000). Furthermore, ART patients with ovarian endometriomata had a statistically significantly increased likelihood of having a SGA baby when compared with other forms of endometriosis. CONCLUSION(S) Rates of preterm birth and SGA babies doubled in infertility patients with ovarian endometriomata who required ART.

Adverse obstetric and perinatal outcomes in subfertile women conceiving without assisted reproductive technologies.

OBJECTIVE To determine whether adverse perinatal outcomes are increased in subfertile women. DESIGN Cohort study. SETTING Two tertiary assisted reproductive technologies (ART) centers; Victorian births register. PATIENT(S) Records of women who registered with the clinics (1991-2000), but did not have an infant using ART, were linked to the birth register (1991-2004) to identify singleton non-ART births within 5 years of registration (N = 2171). Controls, matched by maternal age and year of infants birth, were selected randomly from birth records (N = 4363). INTERVENTIONS None. MAIN OUTCOME MEASURE(S) Adverse obstetric and perinatal outcomes. RESULT(S) After adjusting for confounders, compared with controls, subfertile women had increased odds of hypertension or preeclampsia (adjusted odds ratio [OR] 1.29, 1.02-1.61), antepartum hemorrhage (adjusted OR 1.41, 1.05-1.89), perinatal death (adjusted OR 2.19, 1.10-4.36), low birth weight (adjusted OR 1.44, 1.11-1.85), preterm birth <37 weeks (adjusted OR 1.32, 1.05-1.67) or <31 weeks (adjusted OR 2.37, 1.35-4.13), and cesarean delivery (adjusted OR 1.56, 1.37-1.77). There was weak evidence for increased birth defects (adjusted OR 1.30, 0.98-1.72) and gestational diabetes (adjusted OR 1.25, 0.96-1.63). No increased risk was found for prelabor rupture of membranes, small for gestational age, or postpartum hemorrhage. CONCLUSION(S) Subfertile women with singleton births are at increased risk of several adverse outcomes. These risks should be considered during their antenatal care and when analyzing adverse effects of ART.

Increased risk of blastogenesis birth defects, arising in the first 4 weeks of pregnancy, after assisted reproductive technologies

BACKGROUND The reasons for increased birth defect prevalence following in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are largely unknown. Classification of birth defects by pathology rather than organ system, and examination of the role of embryo freezing and thawing may provide clues to the mechanisms involved. This study aimed to investigate these two factors. METHOD Data on 6946 IVF or ICSI singleton pregnancies were linked to perinatal outcomes obtained from population-based data sets on births and birth defects occurring between 1991 and 2004 in Victoria, Australia. These were compared with 20,838 outcomes for singleton births in the same population, conceived without IVF or ICSI. Birth defects were classified according to pathogenesis. RESULTS Overall, birth defects were increased after IVF or ICSI [adjusted odds ratio (OR) 1.36; 95% CI: 1.19-1.55] relative to controls. There was no strong evidence of risk differences between IVF and ICSI or between fresh and thawed embryo transfer. However, a specific group, blastogenesis birth defects, were markedly increased [adjusted OR 2.80, 95% CI: 1.63-4.81], with the increase relative to the controls being significant for fresh embryo transfer (adjusted OR 3.65; 95% CI: 2.02-6.59) but not for thawed embryo transfer (adjusted OR 1.60; 95% CI: 0.69-3.69). CONCLUSION Our findings suggest that there is a specific risk of blastogenesis birth defects arising very early in pregnancy after IVF or ICSI and that this risk may be lower with use of frozen-thawed embryo transfer.

Pregnancies conceived using assisted reproductive technologies (ART) have low levels of pregnancy-associated plasma protein-A (PAPP-A) leading to a high rate of false-positive results in first trimester screening for Down syndrome

BACKGROUND First trimester screening (FTS) for Down syndrome combines measurement of nuchal translucency, free beta-human chorionic gonadotrophin and pregnancy-associated plasma protein-A (PAPP-A). The aim of this study was to undertake a detailed analysis of FTS results in singleton pregnancies conceived using assisted reproductive technologies (ART) and non-ART pregnancies. METHODS A record linkage study compared outcomes in 1739 ART-conceived and 50 253 naturally conceived pregnancies. RESULTS Overall, significantly lower PAPP-A levels were detected in ART pregnancies (0.83 multiples of median, MoM) than in controls (1.00 MoM) (t-test P < 0.001). This difference remained after excluding complicated pregnancies. Analysis of factors affecting PAPP-A levels suggested fresh compared with frozen embryo transfers and use of artificial cycles compared with natural cycles for frozen transfers were associated with lower values. The adjusted odds ratio (AdjOR) for receiving a false-positive result was 1.71 (95% CI 1.44-2.04; P < 0.001) for ART pregnancies compared with non-ART pregnancies, and this leads to a higher AdjOR (1.24, 95% CI 1.03-1.49; P = 0.02) for having a chorionic villous sampling (CVS) or amniocentesis. CONCLUSIONS ART pregnancies have reduced FTS PAPP-A levels leading to an increased likelihood of receiving a false-positive result and having a CVS/amniocentesis. Lower PAPP-A may reflect impairment of early implantation with some forms of ART.

Using record linkage and manual follow-up to evaluate the Victorian maternal serum screening quadruple test for Down's syndrome, trisomy 18 and neural tube defects.

Objectives: The Genetic Health Services Victoria maternal serum screening (MSS) quadruple test has been available to pregnant women in Victoria since 1996. The objectives of this study were to follow up the pregnancies screened by MSS between July 1998 and June 2000 and to determine the performance characteristics of the test for Downs syndrome, trisomy 18 and neural tube defects (NTDs). Methods: MSS results were matched to pregnancy outcome information from the Perinatal Data Collection Unit and Birth Defects Register, using automated probabilistic record linkage. For unmatched pregnancies, manual follow-up was carried out by contacting referring doctors and hospitals, resulting in a very high follow-up rate of 99.2% (18,989/19,143). Results: The sensitivity of MSS for Downs syndrome was 85% (23/27–95%CI 72–99%) with a falsepositive rate (FPR) of 6.8% (risk threshold ≥ 1 in 250). While using a fixed 5% FPR, the sensitivity for Downs syndrome was slightly lower (78%). The sensitivity for trisomy 18 was 44% (4/9 – 95% CI 12–77%) with a FPR of 0.5% (risk threshold of ≥ 1 in 200). 11 of the 15 (73 – 95%CI 51–97%) cases of open NTDs were detected from screening, with a 1% FPR (risk threshold alpha-fetoprotein [AFP] ≥2.5 MoM). All cases of anencephaly had increased AFP levels. Conclusion: Probabilistic record linkage and manual follow-up is an efficient method for ascertainment of pregnancy outcomes, with a higher follow-up rate than that reported in similar studies. MSS should remain an available option for all pregnant women in Victoria, with test characteristics comparable with other recent reports of the quadruple test.

People who influence women's decisions and preferred sources of information about prenatal testing for birth defects

Background:  More than half of Victorian pregnant women are undergoing prenatal testing for birth defects, although little is known about the factors that are influencing their decisions.

Using population-based data to predict the impact of introducing noninvasive prenatal diagnosis for Down syndrome

Purpose: To compare the number and types of chromosome abnormalities prenatally diagnosed and the number of invasive procedures between current prenatal testing pathways and a pathway where noninvasive prenatal diagnosis for Down syndrome replaces Down syndrome screening tests.Methods: Numbers and types of chromosome abnormalities for each referral category were extracted from prenatal diagnostic testing reports routinely collected in Victoria, Australia, in 2006 and 2007. These data were then applied to the proposed implementation strategy.Results: If noninvasive prenatal diagnosis for Down syndrome had replaced Down syndrome screening tests in 2006 and 2007, in Victoria, there would have been 25 (7%) additional Down syndrome diagnosed, 6896 (84%) fewer invasive procedures, and 231 (56%) non-Down syndrome chromosome abnormalities no longer detected. These include trisomy 13, trisomy 18, sex chromosome abnormalities, balanced and unbalanced rearrangements, polyploidy, and mosaic results.Conclusions: The potential loss of information about chromosome abnormalities other than Down syndrome with noninvasive prenatal diagnosis compared with full karyotyping with traditional prenatal diagnosis should be considered when planning for the implementation of new technologies.

Follow up and evaluation of the Victorian first‐trimester combined screening programme for Down syndrome and trisomy 18

Objective  The objective of this study was to follow up and evaluate the statewide first‐trimester combined screening programme for Down syndrome and trisomy 18 at Genetic Health Services Victoria, Australia.

Uptake of prenatal diagnostic testing and the effectiveness of prenatal screening for Down syndrome

To map prenatal screening and diagnostic testing pathways in Victorian pregnant women during 2003 to 2004; measure the impact of prenatal diagnostic testing uptake on the effectiveness of prenatal screening for Down syndrome; and assess factors influencing uptake of diagnostic testing following screening.