Dataset Information

Effectiveness of modified downregulation for women with moderate and severe adenomyosis of the uterus prior to frozen thawed embryo transfer (MODA) study protocol: a pragmatic randomised-controlled trial.

ABSTRACT:

Introduction

Adenomyosis can adversely reduce chances of pregnancy in couples undergoing assisted conception. We aim to evaluate the effect of two different downregulation protocols on the reproductive outcomes in women with moderate and severe adenomyosis undergoing frozen-thawed embryo transfer (FTET).

Methods and analysis

We will conduct a two-armed pragmatic randomised clinical trial comparing modified downregulation with gonadotrophin-releasing hormone (GnRH) analogue for 6 weeks to standard downregulation with GnRH analogue for 1 week prior to FTET. Our primary outcome is clinical pregnancy, defined as a viable intrauterine pregnancy confirmed by ultrasound at greater than 6 weeks gestation, with other secondary reproductive, neonatal and safety outcomes. We aim to randomise 162 patients over 3 years to achieve 80% power for detecting a 20% difference in the primary outcome at 5% significance.

Ethics and dissemination

To date there is no consensus on the optimal protocol for management of subfertile women with adenomyosis. Modified downregulation could improve the clinical pregnancy rate by reducing the endometrial inflammatory reaction and/or myometrial contractility and their impact on uterine receptivity in women with moderate and severe adenomyosis of the uterus undergoing FTET. The MODA trial is designed to offer pragmatic, real-life evaluation of the optimal protocol for downregulation for this population during assisted conception treatments. Our findings will be published in peer-reviewed journals and presented at national and international scientific meetings and congresses. Ethical approval was granted by the NHS Research Ethics Committees (19/LO/1567).

Trial registration number

NCT03946722.

SUBMITTER: Latif S

PROVIDER: S-EPMC8559114 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Publications

Effectiveness of modified downregulation for women with moderate and severe adenomyosis of the uterus prior to frozen thawed embryo transfer (MODA) study protocol: a pragmatic randomised-controlled trial.

Latif Sania S Wattar Bassel H Al BHA Balachandren Neerujah N Lukaszewski Tomasz T Saridogan Ertan E Yasmin Ephia E Serhal Paul P Mavrelos Dimitrios D

BMJ open 20211029 10

<h4>Introduction</h4>Adenomyosis can adversely reduce chances of pregnancy in couples undergoing assisted conception. We aim to evaluate the effect of two different downregulation protocols on the reproductive outcomes in women with moderate and severe adenomyosis undergoing frozen-thawed embryo transfer (FTET).<h4>Methods and analysis</h4>We will conduct a two-armed pragmatic randomised clinical trial comparing modified downregulation with gonadotrophin-releasing hormone (GnRH) analogue for 6 w ...[more]

PMID: 34716161

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Project description:BackgroundThe aim was to investigate whether children born after assisted reproduction technology (ART), particularly after frozen-thawed embryo transfer (FET), are at higher risk of childhood cancer than children born after fresh embryo transfer and spontaneous conception.Methods and findingsWe performed a registry-based cohort study using data from the 4 Nordic countries: Denmark, Finland, Norway, and Sweden. The study included 7,944,248 children, out of whom 171,774 children were born after use of ART (2.2%) and 7,772,474 children were born after spontaneous conception, representing all children born between the years 1994 to 2014 in Denmark, 1990 to 2014 in Finland, 1984 to 2015 in Norway, and 1985 to 2015 in Sweden. Rates for any cancer and specific cancer groups in children born after each conception method were determined by cross-linking national ART registry data with national cancer and health data registries and population registries. We used Cox proportional hazards models to estimate the risk of any cancer, with age as the time scale. After a mean follow-up of 9.9 and 12.5 years, the incidence rate (IR) of cancer before age 18 years was 19.3/100,000 person-years for children born after ART (329 cases) and 16.7/100,000 person-years for children born after spontaneous conception (16,184 cases). Adjusted hazard ratio (aHR) was 1.08, 95% confidence interval (CI) 0.96 to 1.21, p = 0.18. Adjustment was performed for sex, plurality, year of birth, country of birth, maternal age at birth, and parity. Children born after FET had a higher risk of cancer (48 cases; IR 30.1/100,000 person-years) compared to both fresh embryo transfer (IR 18.8/100,000 person-years), aHR 1.59, 95% CI 1.15 to 2.20, p = 0.005, and spontaneous conception, aHR 1.65, 95% CI 1.24 to 2.19, p = 0.001. Adjustment either for macrosomia, birth weight, or major birth defects attenuated the association marginally. Higher risks of epithelial tumors and melanoma after any assisted reproductive method and of leukemia after FET were observed. The main limitation of this study is the small number of children with cancer in the FET group.ConclusionsChildren born after FET had a higher risk of childhood cancer than children born after fresh embryo transfer and spontaneous conception. The results should be interpreted cautiously based on the small number of children with cancer, but the findings raise concerns considering the increasing use of FET, in particular freeze-all strategies without clear medical indications.Trial registrationTrial registration number: ISRCTN 11780826.

Project description:BackgroundCoronavirus disease 2019 (COVID-19) has raised concerns about its potential effects on human fertility, particularly among individuals undergoing assisted reproductive therapy (ART). However, the impact of COVID-19 on female reproductive and assisted reproductive outcomes is unclear. In this study, we aimed to evaluate the effects of COVID-19 on pregnancy outcomes during frozen-thawed embryo transfer (FET) cycles.MethodsThis retrospective cohort study included 327 enrolled patients who underwent FET cycles at a single reproductive centre. The study group consisted of patients treated between 1 January 2023 and 31 March 2023 who recently recovered from COVID-19. The embryos for transfer were generated prior to COVID-19 infection. The control group consisted of patients treated between 1 January 2021 and 31 March 2021 who were not infected and did not receive a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Demographic and cycle characteristics and outcomes were compared.ResultsA total of 160 recovered women and 167 controls were included. The primary outcome-the live birth rate-was similar between the two groups (43.8% vs. 43.1%, P > 0.05). The secondary outcomes, such as the implantation rates (41.2% vs. 39.3%), biochemical pregnancy rates (56.3% vs. 56.3%), clinical pregnancy rates (52.5% vs. 52.1%), early abortion rates (8.3% vs. 12.6%) and ongoing pregnancy rates (46.9% vs. 44.3%), were also similar (P < 0.05). According to a logistic regression model, the live birth rate did not decrease after SARS-CoV-2 infection after adjusting for confounding factors (adjusted OR (95% CI) = 0.953 (0.597∼1.523)). Regardless of stratification by age or the number of embryos transferred, the differences remained nonsignificant. Subgroup logistic regression demonstrated that the time interval from infection to transplant had no significant influence on the live birth rate.ConclusionsSARS-CoV-2 infection after oocyte retrieval had no detrimental effect on subsequent FET outcomes.

Project description:BackgroundUterine adenomyosis is a benign disease, common among women in their 40 and 50 s, characterised by ectopic endometrial tissue in the uterine myometrial layer. Adenomyosis causes infertility and has a negative effect on the outcomes of in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) embryo transfer (ET) cycles. It has also been reported to have different characteristics depending on the adenomyotic lesion localisation. The effect of its localisation on IVF/ICSI-ET outcomes is unclear. This study aimed to investigate whether adenomyotic lesion localisation, assessed using magnetic resonance imaging (MRI), was associated with outcomes of IVF/ICSI-ET cycles.MethodsThis multicentre, joint, retrospective cohort study analysed the medical records of 67 infertile patients with adenomyosis who underwent IVF/ICSI with fresh and frozen-thawed ET at five participating facilities from January 2012 to December 2016 and for whom MRI data were available. Fifteen patients were excluded; therefore, the MRI data of 52 patients were evaluated by two radiologists. We assessed the localisation of and classified adenomyotic lesions into advanced (invades the full thickness of the uterine myometrium), extrinsic (localised on the serosal side), and intrinsic (localised on the endometrial side) subtypes.ResultsThere were 40 advanced, nine extrinsic, and three intrinsic cases, and the outcomes of 100, 27, and nine ET cycles, respectively, were analysed. Pregnancy loss/clinical pregnancy and live birth rates of the advanced, extrinsic, and intrinsic groups were 64 % (16/25) and 9 % (9/100), 33.3 % (3/9) and 22.2 % (6/27), and 50 % (1/2) and 11.1 % (1/9), respectively. A logistic regression analysis adjusted for age, prior miscarriage, and body mass index showed that the extrinsic group had fewer pregnancy losses (odds ratio 0.06; 95 % confidence interval [CI]: 0.00-0.54, p = 0.026) and more live births (odds ratio 6.05; 95 % CI: 1.41-29.65, p = 0.018) than the advanced group.ConclusionsAdenomyotic lesions exert different effects on IVF/ICSI-ET outcomes. Thus, MRI assessments of adenomyosis in infertile patients are beneficial. Establishment of treatment plans based on adenomyotic lesion localisation should be considered.

Dataset Information

Effectiveness of modified downregulation for women with moderate and severe adenomyosis of the uterus prior to frozen thawed embryo transfer (MODA) study protocol: a pragmatic randomised-controlled trial.

Introduction

Methods and analysis

Ethics and dissemination

Trial registration number

Publications

Effectiveness of modified downregulation for women with moderate and severe adenomyosis of the uterus prior to frozen thawed embryo transfer (MODA) study protocol: a pragmatic randomised-controlled trial.

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