Oocyte donor age has a significant impact on oocyte recipients' cumulative live-birth rate: a population-based cohort study

© 2019 Objective: To study the impact of the donor's and recipient's age on the cumulative live-birth rate (CLBR) in oocyte donation cycles. Design: A population-based retrospective cohort study. Setting: Not applicable. Patient(s): All women using donated oocytes (n = 1,490) in Victoria, Australia, between 2009 and 2015. Intervention(s): None. Main Outcome Measure(s): The association between the donor's and recipient's age and CLBR modeled by multivariate Cox proportional hazard regression with the covariates of male partner's age, recipient parity, and cause of infertility adjusted for, and donor age grouped as <30, 30–34, 35–37, 38–40, and ≥41 years, and recipient age as <35, 35–37, 38–40, 41–42, 43–44, and ≥45 years. Result(s): The mean age of the oocyte donors was 33.7 years (range: 21 to 45 years) with 49% aged 35 years and over. The mean age of the oocyte recipients was 41.4 years (range: 19 to 53 years) with 25.4% aged ≥45 years. There was a statistically significant relationship between the donor's age and the CLBR. The CLBR for recipients with donors aged <30 years and 30–34 years was 44.7% and 43.3%, respectively. This decreased to 33.6% in donors aged 35–37 years, 22.6% in donors aged 38–40 years, and 5.1% in donors aged ≥41 years. Compared with recipients with donors aged <30 years, the recipients with donors aged 38–40 years had 40% less chance of achieving a live birth (adjusted hazard ratio 0.60; 95% CI, 0.43–0.86) and recipients with donors aged ≥41 years had 86% less chance of achieving a live birth (adjusted hazard ratio 0.14; 95% CI, 0.04–0.44). The multivariate analysis showed no statistically significant effect of the recipient's age on CLBR. Conclusion(s): We have demonstrated that the age of the oocyte donor is critical to the CLBR and is independent of the recipient woman's age. Recipients using oocytes from donors aged ≥35 years had a statistically significantly lower CLBR when compared with recipients using oocytes from donors aged <35 years

Having a baby in your 40s with ART: the reproductive dilemma of autologous versus donor oocytes.

BACKGROUND:Increasing numbers of women ≥40 years old are accessing assisted reproductive technology (ART) due to age-related infertility. There is limited population-based evidence about the impact on the cumulative live birth rate (CLBR) of women aged ≥40 years using their own oocytes, compared to women of a similar age, using donor oocytes. AIMS:To compare the CLBR for women ≥40 years undergoing ART using autologous oocytes and women of similar age using donor oocytes. MATERIALS AND METHODS:This population-based retrospective cohort study used data from all women aged ≥40 years undergoing ART with donated (n = 987) or autologous oocytes (n = 19 170) in Victoria, Australia between 2009 and 2016. A discrete-time survival model was used to evaluate the CLBR following ART with donor or autologous oocytes. The odds ratio, adjusted for woman's age; male age; parity; cause of infertility; and the associated 95% confidence intervals (CI), were calculated. The numbers needed to be exposed (NNEs) were calculated from the adjusted odds ratio (aOR) and the CLBR in the autologous group. RESULTS:The CLBR ranged from 28.6 to 42.5% in the donor group and from 12.5% to 1.4% in the autologous group. The discrete-time survival analysis with 95% CI demonstrated significant aOR on CLBR across all ages (range aOR: 2.56, 95% CI: 1.62-4.01 to aOR: 15.40, 95% CI: 9.10-26.04). CONCLUSIONS:Women aged ≥40 years, using donor oocytes had a significantly higher CLBR than women using autologous oocytes. The findings can be used when counselling women ≥40 years about their ART treatment options and to inform public policy

Prediction of an excessive response in in vitro fertilization from patient characteristics and ovarian reserve tests and comparison in subgroups: an individual patient data meta-analysis.

postprin

Combination of gefitinib and methotrexate to treat tubal ectopic pregnancy (GEM3): a multicentre, randomised, double-blind, placebo-controlled trial

BACKGROUND: Tubal ectopic pregnancies can cause substantial morbidity or even death. Current treatment is with methotrexate or surgery. Methotrexate treatment fails in approximately 30% of women who subsequently require rescue surgery. Gefitinib, an epidermal growth factor receptor inhibitor, might improve the effects of methotrexate. We assessed the efficacy of oral gefitinib with methotrexate, versus methotrexate alone, to treat tubal ectopic pregnancy. METHODS: We performed a multicentre, randomised, double-blind, placebo-controlled trial across 50 UK hospitals. Participants diagnosed with tubal ectopic pregnancy were administered a single dose of intramuscular methotrexate (50 mg/m2) and randomised (1:1 ratio) to 7 days of additional oral gefitinib (250 mg daily) or placebo. The primary outcome, analysed by intention to treat, was surgical intervention to resolve the ectopic pregnancy. Secondary outcomes included time to resolution of ectopic pregnancy and serious adverse events. This trial is registered at the ISRCTN registry, ISCRTN 67795930. FINDINGS: Between Nov 2, 2016, and Oct 6, 2021, 328 participants were allocated to methotrexate and gefitinib (n=165) or methotrexate and placebo (n=163). Three participants in the placebo group withdrew. Surgical intervention occurred in 50 (30%) of 165 participants in the gefitinib group and in 47 (29%) of 160 participants in the placebo group (adjusted risk ratio 1·15, 95% CI 0·85 to 1·58; adjusted risk difference -0·01, 95% CI -0·10 to 0·09; p=0·37). Without surgical intervention, median time to resolution was 28·0 days in the gefitinib group and 28·0 days in the placebo group (subdistribution hazard ratio 1·03, 95% CI 0·75 to 1·40). Serious adverse events occurred in five (3%) of 165 participants in the gefitinib group and in six (4%) of 162 participants in the placebo group. Diarrhoea and rash were more common in the gefitinib group. INTERPRETATION: In women with a tubal ectopic pregnancy, adding oral gefitinib to parenteral methotrexate does not offer clinical benefit over methotrexate and increases minor adverse reactions. FUNDING: National Institute of Health Research

Prediction of complications in early-onset pre-eclampsia (PREP): development and external multinational validation of prognostic models.

BACKGROUND: Unexpected clinical deterioration before 34 weeks gestation is an undesired course in early-onset pre-eclampsia. To safely prolong preterm gestation, accurate and timely prediction of complications is required. METHOD: Women with confirmed early onset pre-eclampsia were recruited from 53 maternity units in the UK to a large prospective cohort study (PREP-946) for development of prognostic models for the overall risk of experiencing a complication using logistic regression (PREP-L), and for predicting the time to adverse maternal outcome using a survival model (PREP-S). External validation of the models were carried out in a multinational cohort (PIERS-634) and another cohort from the Netherlands (PETRA-216). Main outcome measures were C-statistics to summarise discrimination of the models and calibration plots and calibration slopes. RESULTS: A total of 169 mothers (18%) in the PREP dataset had adverse outcomes by 48 hours, and 633 (67%) by discharge. The C-statistics of the models for predicting complications by 48 hours and by discharge were 0.84 (95% CI, 0.81-0.87; PREP-S) and 0.82 (0.80-0.84; PREP-L), respectively. The PREP-S model included maternal age, gestation, medical history, systolic blood pressure, deep tendon reflexes, urine protein creatinine ratio, platelets, serum alanine amino transaminase, urea, creatinine, oxygen saturation and treatment with antihypertensives or magnesium sulfate. The PREP-L model included the above except deep tendon reflexes, serum alanine amino transaminase and creatinine. On validation in the external PIERS dataset, the reduced PREP-S model showed reasonable calibration (slope 0.80) and discrimination (C-statistic 0.75) for predicting adverse outcome by 48 hours. Reduced PREP-L model showed excellent calibration (slope: 0.93 PIERS, 0.90 PETRA) and discrimination (0.81 PIERS, 0.75 PETRA) for predicting risk by discharge in the two external datasets. CONCLUSIONS: PREP models can be used to obtain predictions of adverse maternal outcome risk, including early preterm delivery, by 48 hours (PREP-S) and by discharge (PREP-L), in women with early onset pre-eclampsia in the context of current care. They have a potential role in triaging high-risk mothers who may need transfer to tertiary units for intensive maternal and neonatal care. TRIAL REGISTRATION: ISRCTN40384046 , retrospectively registered

Can risk prediction models help us individualise stillbirth prevention? A systematic review and critical appraisal of published risk models.

BACKGROUND: Stillbirth prevention is an international priority - risk prediction models could individualise care and reduce unnecessary intervention, but their use requires evaluation. OBJECTIVES: To identify risk prediction models for stillbirth, and assess their potential accuracy and clinical benefit in practice. SEARCH STRATEGY: MEDLINE, Embase, DH-DATA and AMED databases were searched from inception to June 2019 using terms relevant to stillbirth, perinatal mortality and prediction models. The search was compliant with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. SELECTION CRITERIA: Studies developing and/or validating prediction models for risk of stillbirth developed for application during pregnancy. DATA COLLECTION AND ANALYSIS: Study screening and data extraction were conducted in duplicate, using the CHARMS checklist. Risk of bias was appraised using the PROBAST tool. RESULTS: The search identified 2751 citations. Fourteen studies reporting development of 69 models were included. Variables consistently included were: ethnicity, body mass index, uterine artery Doppler, pregnancy-associated plasma protein and placental growth factor. For almost all models there were significant concerns about risk of bias. Apparent model performance (i.e. in the development dataset) was highest in models developed for use later in pregnancy and including maternal characteristics, and ultrasound and biochemical variables, but few were internally validated and none were externally validated. CONCLUSIONS: Almost all models identified were at high risk of bias. There are first-trimester models of possible clinical benefit in early risk stratification; these require validation and clinical evaluation. There were few later pregnancy models but, if validated, these could be most relevant to individualised discussions around timing of birth. TWEETABLE ABSTRACT: Prediction models using maternal factors, blood tests and ultrasound could individualise stillbirth prevention, but existing models are at high risk of bias.The authors are collaborators in the IPPIC (International Prediction of Pregnancy Complications) stillbirth project, funded by Sands (the Stillbirth and Neonatal Death Society)

Development and validation of prediction models for risk of adverse outcomes in women with early-onset pre-eclampsia: protocol of the prospective cohort PREP study.

Background: Early-onset pre-eclampsia with raised blood pressure and protein in the urine before 34 weeks' gestation is one of the leading causes of maternal deaths in the UK. The benefits to the child from prolonging the pregnancy need to be balanced against the risk of maternal deterioration. Accurate prediction models of risks are needed to plan management. Methods: We aim to undertake a multicentre prospective cohort study (Prediction of Risks in Early onset Pre-eclampsia (PREP)) to develop clinical prediction models in women with early-onset pre-eclampsia, for risk of adverse maternal outcomes by 48 h and by discharge. We will externally validate the models in two independent cohorts with 634 and 216 women. In the secondary analyses, we will assess risk of adverse fetal and neonatal outcomes at birth and by discharge. Discussion: The PREP study will quantify the risk of maternal complications at various time points and provide individualised estimates of overall risk in women with early-onset pre-eclampsia to plan the management. Trial registration: ISRCTN registry, ISRCTN40384046