Assisted reproduction technology (ART) is used worldwide, at increasing rates, and data show that some adverse outcomes occur more frequently than following spontaneous conception (SC). Possible explanatory factors for the well-known adverse perinatal outcome in ART singletons were evaluated. PubMed and Cochrane databases from 1982 to 2012 were searched. Studies using donor or frozen oocytes were excluded, as well as those with no control group or including <100 children. The main outcome measure was preterm birth (PTB defined as delivery <37 weeks of gestation), and a random effects model was used for meta-analyses of PTB. Other outcomes were very PTB, low-birthweight (LBW), very LBW, small for gestational age and perinatal mortality. The search returned 1255 articles and 65 of these met the inclusion criteria. The following were identified as predictors for PTB in singletons: SC in couples with time to pregnancy (TTP) > 1 year versus SC singletons in couples with TTP ≤ 1 year [adjusted odds ratio (AOR) 1.35, 95% confidence interval (CI) 1.22, 1.50]; IVF/ICSI versus SC singletons from subfertile couples (TTP > 1 year; AOR 1.55, 95% CI 1.30, 1.85); conception after ovulation induction and/or intrauterine insemination versus SC singletons where TTP ≤ 1 year (AOR 1.45, 95% CI 1.21, 1.74); IVF/ICSI singletons versus their non-ART singleton siblings (AOR 1.27, 95% CI 1.08, 1.49). The risk of PTB in singletons with a 'vanishing co-twin' versus from a single gestation was AOR of 1.73 (95% CI 1.54, 1.94) in the narrative data. ICSI versus IVF (AOR 0.80, 95% CI 0.69-0.93), and frozen embryo transfer versus fresh embryo transfer (AOR 0.85, 95% CI 0.76, 0.94) were associated with a lower risk of PTB. Subfertility is a major risk factor for adverse perinatal outcome in ART singletons, however, even in the same mother an ART singleton has a poorer outcome than the non-ART sibling; hence, factors related to the hormone stimulation and/or IVF methods per se also may play a part. Further research is required into mechanisms of epigenetic modification in human embryos and the effects of cryopreservation on this, whether milder ovarian stimulation regimens can improve embryo quality and endometrial conditions, and whether longer culture times for embryos has a negative influence on the perinatal outcome.
Sanders JN et al., 2022·Reprod Health·
Open Access
In vitro fertilization (IVF) births contribute to a considerable proportion of preterm birth (PTB) each year. However, there is no formal surveillance of adverse perinatal outcomes for less invasive fertility treatments. The study objective was to describe associations between fertility treatment (in vitro fertilization, intrauterine insemination, usually with ovulation drugs (IUI), or ovulation drugs alone) and preterm birth, compared to no treatment in subfertile women. The Fertility Experiences Study (FES) is a retrospective cohort study conducted at the University of Utah between April 2010 and September 2012. Women with a history of primary subfertility self-reported treatment data via survey and interviews. Participant data were linked to birth certificates and fetal death records to asses for perinatal outcomes, particularly preterm birth. A total 487 birth certificates and 3 fetal death records were linked as first births for study participants who completed questionnaires. Among linked births, 19% had a PTB. After adjustment for maternal age, paternal age, maternal education, annual income, religious affiliation, female or male fertility diagnosis, and duration of subfertility, the odds ratios and 95% confidence intervals (CI) for PTB were 2.17 (CI 0.99, 4.75) for births conceived using ovulation drugs, 3.17 (CI 1.4, 7.19) for neonates conceived using IUI and 4.24 (CI 2.05, 8.77) for neonates conceived by IVF, compared to women with subfertility who used no treatment during the month of conception. A reported diagnosis of female factor infertility increased the adjusted odds of having a PTB 2.99 (CI 1.5, 5.97). Duration of pregnancy attempt was not independently associated with PTB. In restricting analyses to singleton gestation, odds ratios were not significant for any type of treatment. IVF, IUI, and ovulation drugs were all associated with a higher incidence of preterm birth and low birth weight, predominantly related to multiple gestation births.
To compare the risk of preterm delivery, low birth weight, and admission of the newborn to a neonatal intensive care unit (NICU) in women pregnant after fertility treatment and subfertile women with the risk in fertile women. Prospective follow-up study. Aarhus University Hospital, Skejby, Denmark, 1989-2006. PATIENT(S): A total of 20,080 liveborn singletons. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Preterm delivery, low birth weight, and admission of the newborn to a NICU. RESULT(S): After adjustment we found a statistically significantly increased risk of preterm delivery and very preterm delivery in women who conceived after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) compared with fertile women. Compared with fertile women, the risk of preterm delivery and very preterm delivery was not statistically significantly different in women pregnant after non-IVF assisted reproductive treatment (non-IVF ART) or subfertile women. We found no association between IVF/ICSI and the risk of low birth weight at term or admittance to the NICU. CONCLUSION(S): The increased risk of preterm delivery after IVF/ICSI may be due to the fertility treatment or unknown characteristics in the couples who undergo IVF/ICSI.
Abstract What are the obstetric and neonatal clinical implications of large-for-gestational age (LGA) babies conceived after a frozen-thawed embryo transfer (FET)? Besides a lower risk of neonatal hypoglycaemia, obstetric and neonatal risks for FET LGA babies were comparable to those conceived spontaneously or after fresh ET. It has been shown that conception after a FET is an independent risk factor for LGA babies. The underlying physiologic mechanism is still unclear but is likely different to the mechanisms that lead to LGA after fresh embryo transfers or spontaneous conception. As the freeze-all strategy and FETs are becoming increasingly popular, an important clinical question revolves around the significance of this complication both for the mother and the baby and whether the obstetric and neonatal risks differ between LGA babies conceived following FET compared to those conceived after fresh embryo transfer (Fresh) and spontaneously conceived babies (SC). Study design, size, duration
This population-based cohort study is based on the Medically Assisted Reproduction data linkage which is a bespoke data linkage of the Australian ART registry to nine population health datasets including births, hospital admissions, medical services, medications, and deaths. All singleton LGA babies in New South Wales (2009-2017) and the Australian Capital Territory (2009-2016) (N = 81,075) conceived either spontaneously or after fresh or frozen-thawed embryo ART were included. Participants/materials, setting, The LGA births were divided into those conceived a) spontaneously without history of subfertility (SC) (n = 73,321), b) spontaneously with history of subfertility (SC-SubFert) (n = 4,516), c) after fresh ET (Fresh) (n = 1,461) d) after FET (n = 1,777). Relevant obstetric and neonatal outcome data were compared between LGA deliveries following FET and those following Fresh, SC and SC-SubFert while adjusting for important confounders including preexisting comorbidities (diabetes mellitus) and stratified by mode of delivery (vaginal birth-VB vs. cesarean section-CS). Main The caesarean section rate was similar between FET (58.2%) and Fresh LGA babies (57.9%) but significantly higher compared to the SC (39.1%) and SC-SubFert (49.9%) cohorts (p < 0.001). The use of forceps was also significantly (p < 0.001) higher in FET (4.6%) and Fresh (4.7%) LGA babies compared to the SC (3.5%) and SC-SubFert (2.1%) cohorts. Mean APGAR Scores at 1min (range: 8.3-8.4) and 5min (8.9 for all groups) after birth were similar between the four groups (p > 0.05).
In VB, the adjusted risk ratios (aRR) for perineal tear, shoulder dystocia and postpartum haemorrhage, neonatal resuscitation, respiratory distress, transient tachypnea, admission to the NICU, perinatal death and hospitalization in the first 2 years of life were not significantly different between the four groups. The risk of neonatal hypoglycaemia was significantly elevated in the Fresh (aRR: 1.87, 95% CI: 1.16-3.01), SC-SubFert (aRR: 1.55, 95% CI: 1.03-2.34) and SC (aRR: 1.63, 95% CI: 1.11-2.40) compared to the FET LGA babies.
In CS births, no significant differences were detected between the groups compared regarding all outcomes evaluated, apart from neonatal hypoglycaemia where SC LGA babies had significantly elevated risk compared to FET LGA babies (aRR: 1.22, 95% CI: 1.02-1.45). Limitations, As data were sourced from population health registries, some risk of misclassification might be present, although this is unlikely to be systematically different between groups compared. Despite controlling for important confounders, including maternal age at delivery, nulliparity, history of diabetes mellitus and socioeconomic variables, residual bias may still be present. This is the first study evaluating the clinical implications of FET LGA babies, suggesting largely similar risks to other LGA babies. However, the difference in risk of hypoglycemia supports a different pathophysiological mechanism for LGA after FET compared to the one of LGA babies conceived spontaneously and following fresh ET. No
Preston M et al., 2024·European journal of obstetrics, gynecology, and reproductive biology·
Open Access
Preterm Birth (delivery before 37 weeks of gestation) is the leading cause of childhood mortality and is also associated with significant morbidity both in the neonatal period and beyond. The aetiology of spontaneous preterm birth is unclear and likely multifactorial incorporating factors such as infection/inflammation and cervical injury. Placental insufficiency is emerging as an additional contributor to spontaneous preterm delivery; however, the mechanisms by which this occurs are not fully understood. Serum biomarkers and imaging techniques have been investigated as potential predictors of placental insufficiency, however none have yet been found to have a sufficient predictive value. This review examines the evidence for the role of the placenta in preterm birth, preterm prelabour rupture of the membranes and abruption as well as highlighting areas where further research is required.