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.

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Obesity is known to be associated with sub-optimal reproductive performance but its direct effect on the outcome of assisted reproduction techniques (ART) is less clear. This present study aimed to perform a systematic review of the available evidence to assess the effects of obesity on the outcome of ART. A number of observational studies were identified. Interpretation of the results was compromised by variations in the methods used to define overweight and obese populations and inconsistencies in the choice and definition of outcome measures. Compared with women with a BMI of 25 kg/m 2 or less, women with a BMI 25 kg/m 2 have a lower chance of pregnancy following IVF [odds ratio (OR) 0.71, 95% CI: 0.62, 0.81], require higher dose of gonadotrophins (weighed mean differences 210.08, 95% CI: 149.12, 271.05) and have an increased miscarriage rate (OR 1.33, 95% CI: 1.06, 1.68). There is insufficient evidence on the effect of BMI on live birth, cycle cancellation, oocyte recovery and ovarian hyperstimulation syndrome. Further studies with clear entry criteria and uniform reporting of outcomes are needed to investigate the true impact of weight on the outcome of ART.

The results of this cumulative meta-analysis confirm that the decreased risks of small for gestational age, low birth weight and preterm delivery and increased risks of large for gestational age and high birth weight associated with pregnancies conceived from frozen embryos have been consistent in terms of direction and magnitude of effect over several years, with increasing precision around the point estimates. Replication in a number of different populations has provided external validity for the results, for outcomes of birth weight and preterm delivery. Meanwhile, caution should be exercised about embarking on a policy of electively freezing all embryos in IVF as there are increased risks for large for gestational age babies and hypertensive disorders of pregnancy. Therefore, elective freezing should ideally be undertaken in specific cases such as ovarian hyperstimulation syndrome, fertility preservation or in the context of randomised trials.

Traditionally, IVF success rates have been reported in terms of live birth per fresh cycle or embryo transfer. With the increasing use of embryo freezing and thawing it is essential that we report not only outcomes following fresh but also those after frozen embryo transfer as a complete measure of success of an IVF treatment. Most people agree that an individual's chance of having a baby following fresh and frozen embryo transfer should be described as cumulative live birth rate. However, views on the most appropriate parameters required to calculate such an outcome have been inconsistent. There is an additional dimension-time for all frozen embryos to be used up by a couple, which can influence the outcome. Given that cumulative live birth rate is generally perceived to be the preferred reporting system in IVF, it is time to have an international consensus on how this statistic is calculated, reported and interpreted by stakeholders across the world.

BACKGROUND The reproductive impact of adenomyosis and endometriosis is widely researched but the extent of these impacts remains elusive. It has been demonstrated that endometriosis, in particular, is known to result in subfertility but endometriosis and adenomyosis are increasingly linked to late pregnancy complications such as those caused by placental insufficiency. At the molecular level, the presence of ectopic endometrium perturbs the endometrial hormonal, cellular, and immunological milieu, negatively influencing decidualization, placentation, and developmental programming of the embryo. It is unclear if and how such early aberrant reproductive development relates to pregnancy outcomes in endometriosis and adenomyosis. OBJECTIVE AND RATIONALE The aims of this systematic review and meta-analysis were to (i) investigate the association of adenomyosis and endometriosis with fertility, obstetric, and neonatal outcomes of women through both assisted reproduction and natural conception and (ii) determine whether endometriosis disease subtypes have specific impacts on different stages of the reproductive process. SEARCH METHODS A systematic literature review of NHS evidence electronic databases and the Cochrane database identified all comparative and observational studies between 1980 and December 2018 in any language on adenomyosis and endometriosis with fertility, obstetric, and neonatal outcomes (23 search terms used). A total of 104 papers were selected for data extraction and meta-analysis, with use of Downs and Black standardized checklist to evaluate quality and bias. OUTCOMES We found that endometriosis consistently leads to reduced oocyte yield and a reduced fertilization rate (FR), in line with current evidence. Milder forms of endometriosis were most likely to affect the fertilization (FR OR 0.77, CI 0.63–0.93) and earlier implantation processes (implantation rate OR 0.76, CI 0.62–0.93). The more severe disease by American Society for Reproductive Medicine staging (ASRM III and IV) influenced all stages of reproduction. Ovarian endometriosis negatively affects the oocyte yield (MD −1.22, CI −1.96, −0.49) and number of mature oocytes (MD −2.24, CI −3.4, −1.09). We found an increased risk of miscarriage in both adenomyosis and endometriosis (OR 3.40, CI 1.41–8.65 and OR 1.30, CI 1.25–1.35, respectively), and endometriosis can be associated with a range of obstetric and fetal complications including preterm delivery (OR 1.38, CI 1.01–1.89), caesarean section delivery (OR 1.98 CI 1.64–2.38), and neonatal unit admission following delivery (OR 1.29, CI 1.07–1.55). WIDER IMPLICATIONS Adenomyosis and the subtypes of endometriosis may have specific complication profiles though further evidence is needed to be able to draw conclusions. Several known pregnancy complications are likely to be associated with these conditions. The complications are possibly caused by dysfunctional uterine changes leading to implantation and placentation issues and therefore could potentially have far-reaching consequences as suggested by Barker’s hypothesis. Our findings would suggest that women with these conditions should ideally receive pre-natal counselling and should be considered higher risk in pregnancy and at delivery, until evidence to the contrary is available. In order to expand our knowledge of these conditions and better advise on future management of these patients in reproductive and maternal medicine, a more unified approach to studying fertility and reproductive outcomes with longer term follow-up of the offspring and attention to the subtype of disease is necessary.

Background Threatened miscarriage is a common complication in the first trimester of pregnancy and is often associated with anxiety regarding pregnancy outcome.Objective We undertook a systematic review to explore the effects of threatened miscarriage in the first trimester on maternal and perinatal outcomes.Search strategy An electronic literature search using MEDLINE and EMBASE, and bibliographies of retrieved primary articles. No language restrictions were applied.Selection criteria All studies analysing outcomes of first-trimester bleeding where viability was confirmed on ultrasound or the pregnancy continued beyond viability.Data collection and analysis Two review authors independently selected studies and extracted data on study characteristics, quality and accuracy. Meta-analysis was performed using Review Manager softwareMain outcome measures The outcome was broadly categorised into maternal and perinatal outcomes. The chief maternal outcomes included pre-eclampsia/eclampsia or pregnancy-induced hypertension, antepartum haemorrhage, preterm prelabour rupture of membranes (PPROM) and mode of delivery. The perinatal outcomes evaluated were preterm delivery, low birthweight, intrauterine growth restriction, perinatal mortality, indicators of perinatal morbidity (Apgar scores and neonatal unit admission) and presence of congenital anomalies.Main results Fourteen studies met the inclusion criteria. Women with threatened miscarriage had a significantly higher incidence of antepartum haemorrhage due to placenta praevia [odds ratio (OR) 1.62, 95% CI 1.19, 2.22] or antepartum haemorrhage of unknown origin (OR 2.47, 95% CI 1.52, 4.02) when compared with those without first-trimester bleeding. They were more likely to experience PPROM (OR 1.78, 95% CI 1.28, 2.48), preterm delivery (OR 2.05, 95% CI 1.76, 2.4) and to have babies with intrauterine growth restriction (OR 1.54, 95% CI 1.18, 2.00). First-trimester bleeding was associated with significantly higher rates of perinatal mortality (OR 2.15, 95% CI 1.41, 3.27) and low-birthweight babies (OR 1.83, 95% CI 1.48, 2.28).Authors' conclusions Threatened miscarriage in the first trimester is associated with increased incidence of adverse maternal and perinatal outcome.

Analysis 1.2. Comparison 1 Endometrial injury between day 7 of the previous cycle and day 7 of the ET cycle vs control, Outcome 2 Live birth or ongoing pregnancy per randomly assigned woman (by embryo transfer history).. . Analysis 1.3. Comparison 1 Endometrial injury between day 7 of the previous cycle and day 7 of the ET cycle vs control, Outcome 3 Miscarriage per clinical pregnancy.