Fresh ET has been the conventional strategy in IVF, but there is a growing opinion suggesting that its maternal and perinatal outcomes can be enhanced by a policy of elective freezing of embryos, ...followed by transfer at a later date. Available studies suggest a number of improved maternal and perinatal outcomes after frozen ET, although there is also a suggestion of large for gestational age babies associated with this strategy. The observational nature of the available data limit our confidence in the results of available studies. A genuinely unbiased estimate of the advantages of a policy of elective ET can only be confirmed by a definitive randomized controlled trial with an adequate length of follow-up of the offspring.
The prevalence of obesity is increasing worldwide, with a corresponding increase in overweight and obese patients referred with infertility. This systematic review aimed to determine whether ...non-surgical weight reduction strategies result in an improvement in reproductive parameters affected by obesity, e.g. delayed time to pregnancy, oligozoospermia and azoospermia. No prior reviews have examined this within the general fertility population, or in both sexes.
Our objective was to answer the question: 'In overweight and obese women, men and couples seeking fertility treatment, what non-surgical weight-loss interventions have been used, and how effective are they at weight loss and improving reproductive outcomes?'
An electronic search of MEDLINE, EMBASE and the Cochrane Library was performed for studies between January 1966 and March 2016. Text word and MESH search terms used related to infertility, weight and barriers to weight loss. Inclusion criteria were an intervention to change lifestyle evaluated in any study design in participants of either gender with an unfulfilled desire to conceive. Studies were excluded if they included participants not attempting pregnancy, with illnesses that might cause weight fluctuations, or studies evaluating bariatric surgery. Two reviewers performed data extraction and quality assessment using the Cochrane Risk of Bias Tool for randomized trials, and a ratified checklist (ReBIP) for non-randomized studies.
A total of 40 studies were included, of which 14 were randomised control trials. Primary outcomes were pregnancy, live birth rate and weight change. In women, reduced calorie diets and exercise interventions were more likely than control interventions to result in pregnancy risk ratio 1.59, 95% CI (1.01, 2.50), and interventions resulted in weight loss and ovulation improvement, where reported. Miscarriage rates were not reduced by any intervention.
Overweight and obese persons seeking fertility should be educated on the detrimental effects of fatness and the benefits of weight reduction, including improvement in pregnancy rates. A combination of a reduced calorie diet, by reducing fat and refined carbohydrate intake, and increased aerobic exercise should form the basis of programmes designed for such individuals. A lack of randomized studies in men and couples, and studies evaluating barriers to undertaking weight loss in infertile populations is evident, and future research should examine these issues further.
OBJECTIVE: To perform a systematic review and meta-analysis of obstetric and perinatal complications in singleton pregnancies after the transfer of frozen thawed and fresh embryos generated through ...IVF. DESIGN: Systematic review. SETTING: Observational studies, comparing obstetric and perinatal outcomes in singleton pregnancies subsequent to frozen thawed ET versus fresh embryo transfer, were included from Medline, EMBASE, Cochrane Central Register of Clinical Trials, DARE, and CINAHL (1984–2012). PATIENT(S): Women undergoing IVF/intracytoplasmic sperm injection (ICSI). INTERVENTION(S): Two independent reviewers extracted data and assessed the methodological quality of the relevant studies using critical appraisal skills program scoring. Risk ratios and risk differences were calculated in Rev Man 5.1. Subgroup analysis was performed on matched cohort studies. MAIN OUTCOME MEASURE(S): Antepartum hemorrhage, very preterm birth, preterm birth, small for gestational age, low birth weight, very low birth weight, cesarean section, congenital anomalies, perinatal mortality, and admission to neonatal intensive care unit. RESULT(S): Eleven studies met the inclusion criteria. Singleton pregnancies after the transfer of frozen thawed embryos were associated with better perinatal outcomes compared with those after fresh IVF embryos. The relative risks (RR) and 95% confidence intervals (CI) of antepartum hemorrhage (RR = 0.67, 95% CI 0.55–0.81), preterm birth (RR = 0.84, 95% CI 0.78–0.90), small for gestational age (RR = 0.45, 95% CI 0.30–0.66), low birth weight (RR = 0.69, 95% CI 0.62–0.76), and perinatal mortality (RR = 0.68, 95% CI 0.48–0.96) were lower in women who received frozen embryos. CONCLUSION(S): Although fresh ET is the norm in IVF, results of this systematic review of observational studies suggest that pregnancies arising from the transfer of frozen thawed IVF embryos seem to have better obstetric and perinatal outcomes.
Earlier reviews have suggested that IVF/ICSI pregnancies are associated with higher risks. However, there have been recent advances in the way IVF/ICSI is done, leading to some controversy as to ...whether IVF/ICSI singletons are associated with higher perinatal risks. The objective of this systematic review was to provide an up-to-date comparison of obstetric and perinatal outcomes of the singletons born after IVF/ICSI and compare them with those of spontaneous conceptions.
Extensive searches were done by two authors. The protocol was agreed a priori. PRISMA guidance was followed. The data were extracted in 2 × 2 tables. Risk ratio and risk difference were calculated on pooled data using Rev Man 5.1. Quality assessment of studies was performed using Critical Appraisal Skills programme. Sensitivity analysis was performed when the heterogeneity was high (I(2) > 50%).
There were 20 matched cohort studies and 10 unmatched cohort studies included in this review. IVF/ICSI singleton pregnancies were associated with a higher risk (95% confidence interval) of ante-partum haemorrhage (2.49, 2.30-2.69), congenital anomalies (1.67, 1.33-2.09), hypertensive disorders of pregnancy (1.49, 1.39-1.59), preterm rupture of membranes (1.16, 1.07-1.26), Caesarean section (1.56, 1.51-1.60), low birthweight (1.65, 1.56-1.75), perinatal mortality (1.87, 1.48-2.37), preterm delivery (1.54, 1.47-1.62), gestational diabetes (1.48, 1.33-1.66), induction of labour (1.18, 1.10-1.28) and small for gestational age (1.39, 1.27-1.53).
Singletons pregnancies after IVF/ICSI are associated with higher risks of obstetric and perinatal complications when compared with spontaneous conception. Further research is needed to determine which aspect of assisted reproduction technology poses most risk and how this risk can be minimized.
To explore obstetric and perinatal outcomes in singleton pregnancies occurring as a result of fresh and thawed frozen embryo transfer using anonymized Human Fertilisation and Embryology Authority ...data.
Retrospective cohort study.
Not applicable.
Singleton births after IVF/intracytoplasmic sperm injection cycles in the United Kingdom (1991-2011).
A total of 112,432 cycles (95,911 fresh and 16,521 frozen) were analyzed using multivariate logistic regression to explore associations between type of embryo transferred (frozen vs. fresh) and obstetric and perinatal outcomes. Relative risks (RRs) and their 99.5% confidence intervals (CIs) were calculated using Stata 14 MP, adjusting for potential confounders.
Birth weight.
The adjusted RR (99.5% CI) of low birth weight 0.73 (0.66-0.80) and very low birth weight 0.78 (0.63-0.96) were all lower after frozen embryo transfer; however, RR of having a high birth weight baby was higher 1.64 (1.53-1.76). There was no difference in RR of preterm birth 0.96 (0.88-1.03), very preterm birth 0.86 (0.70-1.05), and congenital anomalies 0.86 (0.73-1.01).
The findings of low birth and very low birth weight after thawed frozen embryo transfer are consistent with the literature and provide reassurance regarding the outcome of pregnancies after frozen embryo transfers. However, they highlight the possibility of high birth weight in these babies. Because these results are based on observational data, further evidence from randomized, controlled trials is needed before elective cryopreservation of all embryos is practiced in preference to the current practice of transfer of fresh embryos.
OBJECTIVE: To perform a systematic review and meta-analysis of obstetric and perinatal complications in singleton pregnancies after the transfer of blastocyst-stage and cleavage-stage embryos ...generated through IVF. DESIGN: Systematic review. SETTING: University hospital. PATIENT(S): Singleton pregnancies resulting from ET at the blastocyst stage versus those at the cleavage stage. INTERVENTION(S): Medline, EMBASE, Cochrane Central Register of Clinical Trials DARE, and CINAHL (1980–2013) were searched. Two independent reviewers extracted data and assessed the methodological quality of the relevant studies using CASP scoring. Risk ratios and risk differences were calculated in Rev Man 5.1. MAIN OUTCOME MEASURE(S): Very preterm birth, preterm birth, small for gestational age, low birth weight, very low birth weight, congenital anomalies, perinatal mortality, preeclampsia, and placenta previa. RESULT(S): In vitro fertilization pregnancies occurring as a result of ET at the blastocyst stage were associated with a higher relative risk (RR; 95% confidence interval CI) of preterm (RR 1.27; 95% CI 1.22–1.31) and very preterm delivery (RR 1.22; 95% CI 1.10–1.35) in comparison with those resulting from the transfer of cleavage-stage embryos. The risk of growth restriction was lower in babies conceived through blastocyst transfer (RR 0.82; 95% CI 0.77–0.88). CONCLUSION(S): Data from observational studies show that ET at the blastocyst stage is associated with a higher risk of very preterm delivery. However, we were not able to adjust for confounders. Perinatal outcome data from existing randomized trials are needed to determine the safety of ET at the blastocyst stage compared with the cleavage stage.
Uterine adenomyosis was initially thought to be found only in parous women, and final diagnosis was made at histology after hysterectomy. With better imaging techniques and with women attending ...clinics at older ages, adenomyosis is diagnosed with increasing frequency in women attending infertility clinics. A dozen conservative interventions have been advocated, with variable reports of their impact on fertility. This presents a dilemma for clinicians managing such patients. Hence, this systematic review of adenomyosis was performed to determine (i) the prevalence in a subfertile population, (ii) the accuracy of diagnostic tests, (iii) the efficacy of fertility sparing treatment options and (iv) the reproductive and obstetric/perinatal outcomes in women with adenomyosis.
Systematic searches of various databases were performed independently by two reviewers, and data were extracted according to predefined criteria by two reviewers.
There is little data on the epidemiology of adenomyosis associated with subfertility. Both magnetic resonance imaging and ultrasound are non-invasive tests with equivalent accuracy in diagnosing adenomyosis (area under curve 0.91 and 0.88, respectively). Most studies on treatments have been uncontrolled and outcomes are usually reported in the form of case series. Hence, the true impact of various treatments on fertility is not known. There are variable reports of the impact of adenomyosis on the success of IVF. Increased incidence of preterm labour and premature rupture of membranes has been reported in women with adenomyosis.
Further studies are needed to determine the natural history of adenomyosis and implications for fertility and reproductive outcomes, with and without treatment. Currently, there is no evidence that we should find and treat adenomyosis in patients who wish to conceive.
BACKGROUND
While live birth is the principal clinical outcome following in vitro fertilization (IVF) treatment, the number of eggs retrieved following ovarian stimulation is often used as a surrogate ...outcome in clinical practice and research. The aim of this study was to explore the association between egg number and live birth following IVF treatment and identify the number of eggs that would optimize the IVF outcome.
METHODS
Anonymized data on all IVF cycles performed in the UK from April 1991 to June 2008 were obtained from the Human Fertilization and Embryology Authority (HFEA). We analysed data from 400 135 IVF cycles. A logistic model was fitted to predict live birth using fractional polynomials to handle the number of eggs as a continuous independent variable. The prediction model, which was validated on a separate HFEA data set, allowed the estimation of the probability of live birth for a given number of eggs, stratified by age group. We produced a nomogram to predict the live birth rate (LBR) following IVF based on the number of eggs and the age of the female.
RESULTS
The median number of eggs retrieved per cycle was 9 inter-quartile range (IQR) 6–13. The overall LBR was 21.3% per fresh IVF cycle. There was a strong association between the number of eggs and LBR; LBR rose with an increasing number of eggs up to ∼15, plateaued between 15 and 20 eggs and steadily declined beyond 20 eggs. During 2006–2007, the predicted LBR for women with 15 eggs retrieved in age groups 18–34, 35–37, 38–39 and 40 years and over was 40, 36, 27 and 16%, respectively. There was a steady increase in the LBR per egg retrieved over time since 1991.
CONCLUSION
The relationship between the number of eggs and live birth, across all female age groups, suggests that the number of eggs in IVF is a robust surrogate outcome for clinical success. The results showed a non-linear relationship between the number of eggs and LBR following IVF treatment. The number of eggs to maximize the LBR is ∼15.
The increasing prevalence of obesity in young women is a major public health concern. These trends have a major impact on pregnancy outcomes in these women, which have been documented by several ...researchers. In a population based cohort study, using routinely collected data, this paper examines the effect of increasing Body Mass Index (BMI) on pregnancy outcomes in nulliparous women delivering singleton babies.
This was a retrospective cohort study, based on all nulliparous women delivering singleton babies in Aberdeen between 1976 and 2005. Women were categorized into five groups--underweight (BMI < 20 Kg/m2), normal (BMI 20-24.9 Kg/m2) overweight (BMI 25-29.9 Kg/m2), obese (BMI 30-34.9 Kg/m2) and morbidly obese (BMI > 35 Kg/m2). Obstetric and perinatal outcomes were compared by univariate and multivariate analyses.
In comparison with women of BMI 20-24.9, morbidly obese women faced the highest risk of pre-eclampsia {OR 7.2 (95% CI 4.7, 11.2)} and underweight women the lowest {OR 0.6 (95% CI 0.5, 0.7)}. Induced labour was highest in the morbidly obese {OR 1.8 (95% CI 1.3, 2.5)} and lowest in underweight women {OR 0.8 (95% CI 0.8, 0.9)}. Emergency Caesarean section rates were highest in the morbidly obese {OR 2.8 (95% CI 2.0, 3.9)}, and comparable in women with normal and low BMI. Obese women were more likely to have postpartum haemorrhage {OR 1.5 (95% CI 1.3, 1.7)} and preterm delivery (< 33 weeks) {OR 2.0 (95% CI 1.3, 2.9)}. Birthweights less than 2,500 g were more common in underweight women {OR 1.7 (95% OR 1.2, 2.0)}. The highest risk of birth weights > 4,000 g was in the morbidly obese {OR 2.1 (95% CI 1.3, 3.2)} and the lowest in underweight women {OR 0.5 (95% CI 0.4, 0.6)}.
Increasing BMI is associated with increased incidence of pre-eclampsia, gestational hypertension, macrosomia, induction of labour and caesarean delivery; while underweight women had better pregnancy outcomes than women with normal BMI.
In-vitro fertilization (IVF) is the treatment of choice for unresolved infertility. It comprises a number of key steps, each of which has to be negotiated before the next is attempted, but the ...factors which are associated with failure at each stage have not been reported.
We analyzed anonymised national data on women undergoing their first fresh autologous IVF and intracytoplasmic sperm injection (ICSI) cycle in the United Kingdom between 2000 and 2007 to predict factors associated with overall lack of livebirth as well as the chance of non-progress at different stages of an IVF cycle. A total of 121,744 women were included in this analysis. Multivariable models underlined the importance of increased female age and duration of infertility, lack of previous pregnancy, and a diagnosis of tubal or male factor infertility in predicting the risk of not having a live birth in an IVF treatment. At each stage, a woman's chance of proceeding to the next stage of IVF treatment is affected by increased age and duration of infertility. The intention to use intra-cytoplasmic sperm injection (ICSI) is associated with a decreased risk of treatment failure in women starting an IVF cycle (RR 0.93, 99% CI 0.92, 0.94) but this association is reversed at a later stage once fertilisation has been confirmed (RR=1.01, 99%CI 1.00, 1.03).
Female age is a key predictor of failure to have a livebirth following IVF as well as the risk of poor performance at each stage of treatment. While increased duration of infertility is also associated with worse outcomes at every stage, its impact appears to be less influential. Women embarking on ICSI treatment for male factor infertility have a lower chance of treatment failure but this does not appear to be due to increased chances of implantation of ICSI embryos.
PDF
