General Health & Hospital Admissions in Children Born after ART; A Population Based Linkage Study

University College London (UCL) requires access to data on maternal age at the time of birth for the existing study cohorts, consisting of children conceived after Artificial Reproductive Therapies (ART), related spontaneously conceived sibling controls, and unrelated matched spontaneously conceived population controls.

Maternal age at the time of birth has been shown to significantly influence health outcomes in children. For example, several studies have shown that teenage pregnancies often result in infants with lower birth-weight, a greater risk of intrauterine growth restriction, preterm delivery and other adverse outcomes. While older maternal age is often associated with increased risk of preterm delivery, abnormal foetal presentation (such as spontaneous breech presentation), neonatal intraventricular haemorrhage, and increased risk of maternal cardiometabolic disease.

The aim of the study is to establish if children born after assisted conception (including IVF and related techniques) are at an increased risk of specific diagnoses compared to spontaneously conceived siblings and unrelated spontaneously conceived controls. Therefore, in this context, adjustment for key confounding factors such as maternal age at the time of birth is essential, particularly when analysing differences between ART and naturally conceived children in order to elucidate relative contribution of ART treatments and parental characteristics towards perinatal risks.

This project has already yielded the three cohorts mentioned above, and initial data management has been completed.

No amendments to the research design, methodology or the scientific value of the study have been made since this was last reviewed by IGARD and NHS England.

UCL is the controller as the organisation responsible for ensuring that the data will only be processed for the purpose described above.

The lawful basis for processing personal data under the UK GDPR is:

Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller;

The lawful basis for processing special category data under the UK GDPR is:

Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject.

It is in the public interest because the programme of research facilitates the conduct of clinically relevant research into establishing if children born after assisted conception (including IVF and related techniques) are at an increased risk of specific diagnoses compared to spontaneously conceived siblings and unrelated spontaneously conceived controls.

Amazon Web Services (AWS) is a processor acting under the instructions of UCL. AWS’ role is limited to secure back-up of data stored in UCL’s Data Safe Haven.

UCL uses offsite data centre services provided by VIRTUS data centre. VIRTUS does not have access to the data.

UCL (Great Ormond Street Institute of Child Health) aim to establish if children born after assisted conception (including IVF and related techniques) are at an increased risk of specific diagnoses compared to spontaneously conceived siblings and unrelated spontaneously conceived controls.

The diagnoses which are to be investigated include:

a) Complications of Prematurity (such as respiratory distress syndrome, necrotizing enterocolitis, retinopathy of prematurity, intra-ventricular haemorrahges, per-ventricular leucomalacia)

b) Cerebral palsy

c) Congenital malformations

d) Asthma and allergic disease

e) Developmental delay/ and neuro-developmental problems

f) Death

g) Hospitalization rates and length of stay

These comparisons will help to provide robust risk estimates for this ever growing population. This is important as all of these potential risks have been suggested by previous research but have never been confirmed, as previous studies lacked the necessary power and design to do so.

The study cohorts, Artificial Reproductive Therapies (ART), related spontaneously conceived sibling controls, and unrelated matched spontaneously conceived population controls, have been created using the criteria described in section 5b. The cohort numbers are 86,000 (ART Cohort), 23,000 (Sibling Cohort), and 172,000 (Controls Cohort).

Pseudonymised Hospital Episodes Statistics (HES) datasets (Outpatients, Admitted Patient care, Critical Care and A&E) and ONS mortality for the three study cohorts have been disseminated to UCL under a previous version of this agreement.

Manipulations carried out during ART treatment, including both supra-physiological ovarian stimulation and the manipulation of gametes and embryos in vitro, may lead to an increased risk of various adverse health outcomes in children born after ART. The Hospital Episode Statistics (HES) national database will be used to examine general health outcomes & hospital admissions (with an emphasis on long-term health outcomes e.g. burdens of peri-natal complications) in the three cohorts. Primary analyses will consider hospital admissions and recorded diagnoses, and further analyses will consider multiple admissions, length of stay and recorded medical interventions, stratifying for specific cause of infertility and type or means of assisted conception and whether conception arose from a fresh or frozen thawed embryo. Output variables will include all-cause and cause specific hospital admissions and recorded diagnoses, including all-cause and cause specific perinatal morbidity, congenital anomalies, cerebral palsy and epilepsy.

The rates of specific diagnoses will be compared to equivalent rates in both the matched and sibling control groups. In the first instance this will consider conditions chosen a priori including: Complications of Prematurity (Respiratory Distress Syndrome, Necrotising Enterocolitis, Retinopathy of Prematurity, Intra-ventricular Haemorrhage, Peri-ventricular Leucomalacia), Cerebral Palsy, Congenital malformations, Asthma, Allergic disease. Further analysis will consider multiple admissions, length of stay and recorded medical interventions. Subgroup analyses will stratify for duration and cause of parental infertility and type of ART (including fresh vs. cryopreserved cycles).

UCL does not require identifiable data from NHS England and will not pass any data on to third parties, including the HFEA.

Fertility clinics have been engaged in a campaign to inform patients of how their data may be used for research and how they could opt out. Families connected to ART have been consulted on what they would like research to achieve. These service user views are incorporated in UCL's study design.

This study is currently funded by the Wellcome Trust via an Individual Investigator Award in Science. The Wellcome Trust has no role in the design or conduct of the study, and will not be processing or accessing any data.

The expected output includes completion of a scientific paper detailing robust risk estimates of the incidence of perinatal outcomes in children born after ART. Data analysis for this is currently underway and the manuscript is expected to be ready for submission by mid-2023. It is expected that this paper will be submitted to a broad medical peer-reviewed journal which may or may not be subscription only; however, abstracts of this work will be open access. The primary audience for these papers will be a scientific/ clinical audience, in order for clinicians to disseminate results to their service users. It is not possible to say exactly which journal will be the appropriate one for submission of these reports as this depends to some extent on the results of the study. However, previous findings from this study have been published in BMJ Open and the American Journal of Obstetrics and Gynecology, and it is expected that this report will also be submitted to a journal of similar quality and impact factor.

Findings will also be presented at the European Society of Human Reproduction and Embryology conference.

Additionally, the findings of this study will also be disseminated via a study website (https://liftresearchucl.com/)

Finally, a report detailing study findings will be prepared and submitted to the HFEA upon completion of all planned data analyses (target date early 2024).

This project has already produced the benefit of linking cohort members and their mothers, which has also enabled restricted access to more reliable identifiers of cohort members than was originally available from the HFEA. As per original data sharing agreement, these identifiers are currently being held by NHS England securely, but would allow future researchers to undertake important linkage work not possible before this project (when only very limited cohort identifiers were held by the HFEA despite their mandate to collect such comprehensive data). Such future access is subject to approvals from HFEA, CAG, HRA and NHS England. UCL have no access to this data. Initial data analysis has been completed and a cohort profile paper has been published in BMJ Open (10.1136/bmjopen-2021-050931). Creation of this cohort will allow longitudinal monitoring of health and also facilitate exploration of additional outcomes through further linkages in the future.

Analysis of general health outcomes and hospital admissions has also been completed and a manuscript has been submitted to the American Journal of Obstetrics and Gynaecology and is currently undergoing peer review. The findings of this study showed that children born after ART were more likely to be hospitalized compared to those that are naturally conceived, with possible explanations including parental factors including underlying subfertility and increased concern. The initial findings of this study were presented at the Royal College of Paediatrics and Child Health conference in 2021 and the International Population Data Linkage Network conference in 2022. Additionally, the findings have also been presented at various in-house symposia and seminars held within UCL and also shared via the study website (https://liftresearchucl.com).

Analysis for the third paper comparing perinatal outcomes is currently underway. Manuscript preparation has commenced and an initial draft has been shared with team members for feedback. UCL expect it to be ready for submission to a journal by mid-2023.

The findings of these analyses will allow UCL to contextualize levels and trends of disease burden and hospitalization, contribute to prevention and targeted intervention efforts through risk stratification and identification of at-risk individuals or families, develop a better understanding of prognosis, contribute to policy development in the UK, inform existing health services, and allow wider health system resource planning and anticipation of future health resource needs.

University College London (UCL) are requesting access to data on maternal age at the time of birth for the existing study cohorts, consisting of children conceived after Artificial Reproductive Therapies (ART), related spontaneously conceived sibling controls, and unrelated matched spontaneously conceived population controls.

Maternal age at the time of birth has been shown to significantly influence health outcomes in children. For example, several studies have shown that teenage pregnancies often result in infants with lower birth-weight, a greater risk of intrauterine growth restriction, preterm delivery and other adverse outcomes. While older maternal age is often associated with increased risk of preterm delivery, abnormal foetal presentation (such as spontaneous breech presentation), neonatal intraventricular haemorrhage, and increased risk of maternal cardiometabolic disease.

The aim of the study is to establish if children born after assisted conception (including IVF and related techniques) are at an increased risk of specific diagnoses compared to spontaneously conceived siblings and unrelated spontaneously conceived controls. Therefore, in this context, adjustment for key confounding factors such as maternal age at the time of birth is essential, particularly when analysing differences between ART and naturally conceived children in order to elucidate relative contribution of ART treatments and parental characteristics towards perinatal risks.

UCL are requesting an extension of the agreement to allow further time to process this data. This project has already yielded the three cohorts mentioned above, and initial data management has been completed. However, due to the poor data quality of the maternal age at the time of birth data on the Hospital Episode Statistics dataset (>50% missing data), further data processing has been delayed considerably.

No amendments to the research design, methodology or the scientific value of the study have been made since this was last reviewed by IGARD and NHS Digital.

The legal basis for processing personal data for this purpose data at UCL falls under Article 6(1)(e) of the General Data Protection Regulations (GDPR), i.e. “a task carried out in the public interest”. It also falls under Article 9(2)(j), “processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes”. It is in the public interest because the programme of research facilitates the conduct of clinically relevant research into establishing if children born after assisted conception (including IVF and related techniques) are at an increased risk of specific diagnoses compared to spontaneously conceived siblings and unrelated spontaneously conceived controls.

UCL are the sole Data Controller who also process data.

UCL (Great Ormond Street Institute of Child Health) wish to establish if children born after assisted conception (including IVF and related techniques) are at an increased risk of specific diagnoses compared to spontaneously conceived siblings and unrelated spontaneously conceived controls.

The diagnoses which are to be investigated include:

a) Complications of Prematurity (such as respiratory distress syndrome, necrotizing enterocolitis, retinopathy of prematurity, intra-ventricular haemorrahges, per-ventricular leucomalacia)

b) Cerebral palsy

c) Congenital malformations

d) Asthma and allergic disease

e) Developmental delay/ and neuro-developmental problems

f) Death

g) Hospitalization rates and length of stay

These comparisons will help to provide robust risk estimates for this ever growing population. This is important as all of these potential risks have been suggested by previous research but have never been confirmed, as previous studies lacked the necessary power and design to do so.

The study cohorts, Artificial Reproductive Therapies (ART), related spontaneously conceived sibling controls, and unrelated matched spontaneously conceived population controls, have been created using the criteria described in section 5b. The cohort numbers are 86,000 (ART Cohort), 23,000 (Sibling Cohort), and 172,000 (Controls Cohort).

Pseudonymised Hospital Episodes Statistics (HES) datasets (Outpatients, Admitted Patient care, Critical Care and A&E) and ONS mortality for the three study cohorts have been disseminated to UCL under a previous version of this agreement.

Manipulations carried out during ART treatment, including both supra-physiological ovarian stimulation and the manipulation of gametes and embryos in vitro, may lead to an increased risk of various adverse health outcomes in children born after ART. The Hospital Episode Statistics (HES) national database will be used to examine general health outcomes & hospital admissions (with an emphasis on long-term health outcomes e.g. burdens of peri-natal complications) in the three cohorts. Primary analyses will consider hospital admissions and recorded diagnoses, and further analyses will consider multiple admissions, length of stay and recorded medical interventions, stratifying for specific cause of infertility and type or means of assisted conception and whether conception arose from a fresh or frozen thawed embryo. Output variables will include all-cause and cause specific hospital admissions and recorded diagnoses, including all-cause and cause specific perinatal morbidity, congenital anomalies, cerebral palsy and epilepsy.

The rates of specific diagnoses will be compared to equivalent rates in both the matched and sibling control groups. In the first instance this will consider conditions chosen a priori including: Complications of Prematurity (Respiratory Distress Syndrome, Necrotising Enterocolitis, Retinopathy of Prematurity, Intra-ventricular Haemorrhage, Peri-ventricular Leucomalacia), Cerebral Palsy, Congenital malformations, Asthma, Allergic disease. Further analysis will consider multiple admissions, length of stay and recorded medical interventions. Subgroup analyses will stratify for duration and cause of parental infertility and type of ART (including fresh vs. cryopreserved cycles).

UCL is not requesting identifiable data from NHS Digital and will not pass any data on to third parties, including the HFEA.

Fertility clinics have been engaged in a campaign to inform patients of how their data may be used for research and how they could opt out. Families connected to ART have been consulted on what they would like research to achieve. These service user views are incorporated in UCL's study design.

This study is currently funded by the Wellcome Trust via an Individual Investigator Award in Science. The Wellcome Trust has no role in the design or conduct of the study, and will not be processing or accessing any data.

The expected output includes completion of a scientific paper detailing robust risk estimates of the incidence of perinatal outcomes in children born after ART. Data analysis for this is currently underway and the manuscript is expected to be ready for submission by the end of 2022. It is expected that this paper will be submitted to a broad medical peer-reviewed journal which may or may not be subscription only; however, abstracts of this work will be open access. The primary audience for these papers will be a scientific/ clinical audience, in order for clinicians to disseminate results to their service users. It is not possible to say exactly which journal will be the appropriate one for submission of these reports as this depends to some extent on the results of the study. However, previous findings from this study have been published in BMJ Open and the American Journal of Obstetrics and Gynecology, and it is expected that this report will also be submitted to a journal of similar quality and impact factor.

Findings will also be presented at the European Society of Human Reproduction and Embryology conference.

Additionally, the findings of this study will also be disseminated via a study website. This is currently under development and is expected to be completed by October 2022.

Finally, a report detailing study findings will be prepared and submitted to the HFEA upon completion of all planned data analyses (target date early 2023).

This project has already produced the benefit of linking cohort members and their mothers, which has also enabled restricted access to more reliable identifiers of cohort members than was originally available from the HFEA. As per original data sharing agreement, these identifiers are currently being held by NHS-Digital securely, but would allow future researchers to undertake important linkage work not possible before this project (when only very limited cohort identifiers were held by the HFEA despite their mandate to collect such comprehensive data). Such future access is subject to approvals from HFEA, CAG, HRA and NHS-Digital. UCL have no access to this data. Initial data analysis has been completed and a cohort profile paper has been published in BMJ Open (10.1136/bmjopen-2021-050931). Creation of this cohort will allow longitudinal monitoring of health and also facilitate exploration of additional outcomes through further linkages in the future.

Analysis of general health outcomes and hospital admissions has also been completed and a manuscript has been submitted to the American Journal of Obstetrics and Gynaecology and is currently undergoing peer review. The findings of this study showed that children born after ART were more likely to be hospitalized compared to those that are naturally conceived, with possible explanations including parental factors including underlying subfertility and increased concern. The initial findings of this study were presented at the Royal College of Paediatrics and Child Health conference in 2021 and will also presented at the International Population Data Linkage Network conference to be held later this year. Analysis for the third paper comparing perinatal outcomes is currently underway and will be submitted for publication later this year.

The findings of these analyses will allow UCL to contextualize levels and trends of disease burden and hospitalization, contribute to prevention and targeted intervention efforts through risk stratification and identification of at-risk individuals or families, develop a better understanding of prognosis, contribute to policy development in the UK, inform existing health services, and allow wider health system resource planning and anticipation of future health resource needs.

University College London (UCL) are requesting access to data on maternal age at the time of birth for the existing study cohorts, consisting of children conceived after Artificial Reproductive Therapies (ART), related spontaneously conceived sibling controls, and unrelated matched spontaneously conceived population controls.

Maternal age at the time of birth has been shown to significantly influence health outcomes in children. For example, several studies have shown that teenage pregnancies often result in infants with lower birth-weight, a greater risk of intrauterine growth restriction, preterm delivery and other adverse outcomes. While older maternal age is often associated with increased risk of preterm delivery, abnormal foetal presentation (such as spontaneous breech presentation), neonatal intraventricular haemorrhage, and increased risk of maternal cardiometabolic disease.

The aim of the study is to establish if children born after assisted conception (including IVF and related techniques) are at an increased risk of specific diagnoses compared to spontaneously conceived siblings and unrelated spontaneously conceived controls. Therefore, in this context, adjustment for key confounding factors such as maternal age at the time of birth is essential, particularly when analysing differences between ART and naturally conceived children in order to elucidate relative contribution of ART treatments and parental characteristics towards perinatal risks.

Additionally, UCL are also requesting a one-year extension of the agreement to allow further time to process this data, once it has been made available. This project has already yielded the three cohorts mentioned above, and initial data management has been completed. However, due to the poor data quality of the maternal age at the time of birth data on the Hospital Episode Statistics dataset (>50% missing data), further data processing has been delayed considerably. Therefore, UCL now request access to this variable only from the birth registrations dataset for the three study cohorts, along with an extension that will allow UCL the time to carry out the further data processing.

No amendments to the research design, methodology or the scientific value of the study have been made since this was last reviewed by IGARD and NHS Digital.

The legal basis for processing personal data for this purpose data at UCL falls under Article 6(1)(e) of the General Data Protection Regulations (GDPR), i.e. “a task carried out in the public interest”. It also falls under Article 9(2)(j), “processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes”. It is in the public interest because the programme of research facilitates the conduct of clinically relevant research into establishing if children born after assisted conception (including IVF and related techniques) are at an increased risk of specific diagnoses compared to spontaneously conceived siblings and unrelated spontaneously conceived controls.

UCL are the sole Data Controller who also process data.

UCL (Great Ormond Street Institute of Child Health) wish to establish if children born after assisted conception (including IVF and related techniques) are at an increased risk of specific diagnoses compared to spontaneously conceived siblings and unrelated spontaneously conceived controls.

The diagnoses which are to be investigated include:

a) Complications of Prematurity (such as respiratory distress syndrome, necrotizing enterocolitis, retinopathy of prematurity, intra-ventricular haemorrahges, per-ventricular leucomalacia)

b) Cerebral palsy

c) Congenital malformations

d) Asthma and allergic disease

e) Developmental delay/ and neuro-developmental problems

f) Death

g) Hospitalization rates and length of stay

These comparisons will help to provide robust risk estimates for this ever growing population. This is important as all of these potential risks have been suggested by previous research but have never been confirmed, as previous studies lacked the necessary power and design to do so.

The study cohorts, Artificial Reproductive Therapies (ART), related spontaneously conceived sibling controls, and unrelated matched spontaneously conceived population controls, have been created using the criteria described in section 5b. The cohort numbers are 86,000 (ART Cohort), 23,000 (Sibling Cohort), and 172,000 (Controls Cohort).

Psuedonymised Hospital Episodes Statistics (HES) datasets (Outpatients, Admitted Patient care, Critical Care and A&E) and ONS mortality for the three study cohorts have been disseminated to UCL under a previous version of this agreement.

Manipulations carried out during ART treatment, including both supra-physiological ovarian stimulation and the manipulation of gametes and embryos in vitro, may lead to an increased risk of various adverse health outcomes in children born after ART. The Hospital Episode Statistics (HES) national database will be used to examine general health outcomes & hospital admissions (with an emphasis on long-term health outcomes e.g. burdens of peri-natal complications) in the three cohorts. Primary analyses will consider hospital admissions and recorded diagnoses, and further analyses will consider multiple admissions, length of stay and recorded medical interventions, stratifying for specific cause of infertility and type or means of assisted conception and whether conception arose from a fresh or frozen thawed embryo. Output variables will include all-cause and cause specific hospital admissions and recorded diagnoses, including all-cause and cause specific perinatal morbidity, congenital anomalies, cerebral palsy and epilepsy.

The rates of specific diagnoses will be compared to equivalent rates in both the matched and sibling control groups. In the first instance this will consider conditions chosen a priori including: Complications of Prematurity (Respiratory Distress Syndrome, Necrotising Enterocolitis, Retinopathy of Prematurity, Intra-ventricular Haemorrhage, Peri-ventricular Leucomalacia), Cerebral Palsy, Congenital malformations, Asthma, Allergic disease. Further analysis will consider multiple admissions, length of stay and recorded medical interventions. Subgroup analyses will stratify for duration and cause of parental infertility and type of ART (including fresh vs. cryopreserved cycles).

UCL is not requesting identifiable data from NHS Digital and will not pass any data on to third parties, including the HFEA.

Fertility clinics have been engaged in a campaign to inform patients of how their data may be used for research and how they could opt out. Families connected to ART have been consulted on what they would like research to achieve. These service user views are incorporated in UCL's study design.

This study is currently funded by the Wellcome Trust via an Individual Investigator Award in Science. The Wellcome Trust has no role in the design or conduct of the study, and will not be processing or accessing any data.

Outputs will contain only aggregate level data with small numbers suppressed in line with the HES analysis guidance.

The expected outputs from this project include a number of scientific papers, detailing robust risk estimates for the outcomes under investigation (including hospitalization incidence, and incidence of specific diagnoses). It is expected these papers will be submitted by early 2021 and published shortly afterwards.

It is expected that these papers will be submitted to broad medical peer-reviewed journals which may or may not be subscription only, however abstracts of this work will be open access. The main audience for these papers will be a scientific/ clinical audience, in order that clinicians disseminate results to their service users.

Additionally the study will produce a report for the HFEA to publish open access on their website and disseminate via their networks (the fertility clinics, clinicians and directly to patients via these clinics and their website) aiming for September 2021.

It is aimed to also submit abstracts to the Royal College of Paediatrics and Child Health to further publicise results.

It is not possible to say exactly which journal will be the appropriate one for submission of these reports as this depends to some extent to the results the study will find. However, it is expected that these will be high quality journals. For example, work previously done linking this dataset to national cancer registries was published by the New England Journal of Medicine which has the highest impact factor of any medical journal (impact factor 59.6). (http://www.nejm.org/doi/full/10.1056/NEJMoa1301675#t=article). Further work undertaken in partnership with NHS-Digital is due to be published in the BMJ.

Findings will also be presented at the European Society of Human Reproduction and Embryology conference.

The receipt of all data and data linkage processes have taken much longer than expected. The main benefits will be delivered once the dataset is analysed and outputs are produced.

This project has already produced the benefit of linking cohort members and their mothers, which has also enabled restricted access to more reliable identifiers of cohort members than was originally available from the HFEA. As per original data sharing agreement, these identifiers are currently being held by NHS-Digital securely, but would allow future researchers to undertake important linkage work not possible before this project (when only very limited cohort identifiers were held by the HFEA despite their mandate to collect such comprehensive data). Such future access is subject to approvals from HFEA, CAG, HRA and NHS-Digital. UCL have no access to this data.

University College London (UCL) are requesting an extension to allow further time to process the data. Delays occurred in receiving all the required data at the start of the project which delayed the start of the planned data processing time. No amendments to the research design, methodology or the scientific value of the study have been made.

UCL (Great Ormond Street Institute of Child Health) wish to establish if children born after assisted conception (including IVF and related techniques) are at an increased risk of specific diagnoses compared to spontaneously conceived siblings and unrelated spontaneously conceived controls.

The diagnoses which are to be investigated include:

a) Complications of Prematurity (such as respiratory distress syndrome, necrotizing enterocolitis, retinopathy of prematurity, intra-ventricular haemorrahges, per-ventricular leucomalacia)

b) Cerebral palsy

c) Congenital malformations

d) Asthma and allergic disease

e) Developmental delay/ and neuro-developmental problems

f) Death

g) Hospitalization rates and length of stay

These comparisons will help to provide robust risk estimates for this ever growing population. This is important as all of these potential risks have been suggested by previous research but have never been confirmed, as previous studies lacked the necessary power and design to do so.

UCL is not requesting identifiable data from NHS Digital and will not pass any data on to third parties, including the HFEA.

Fertility clinics have been engaged in a campaign to inform patients of how their data may be used for research and how they could opt out. Families connected to ART have been consulted on what they would like research to achieve. These service user views are incorporated in UCL's study design.

Outputs will contain only aggregate level data with small numbers suppressed in line with the HES analysis guidance.

The expected outputs from this project include a number of scientific papers, detailing robust risk estimates for the outcomes under investigation (including hospitalization incidence, and incidence of specific diagnoses). It is expected these papers will be submitted by the end 2019 and published shortly afterwards.

It is expected that these papers will be submitted to broad medical peer-reviewed journals which may or may not be subscription only, however abstracts of this work will be open access. The main audience for these papers will be a scientific/ clinical audience, in order that clinicians disseminate results to their service users.

Additionally the study will produce a report for the HFEA to publish open access on their website and disseminate via their networks (the fertility clinics, clinicians and directly to patients via these clinics and their website) aiming for September 2019 - 2 years after receiving data from NHS- Digital.

It is aimed to also submit abstracts to the Royal College of Paediatrics and Child Health to further publicise results.

It is not possible to say exactly which journal will be the appropriate one for submission of these reports as this depends to some extent to the results the study will find. However, it is expected that these to be high quality journals. For example, work previously done linking this dataset to national cancer registries was published by the New England Journal of Medicine which has the highest impact factor of any medical journal (impact factor 59.6). (http://www.nejm.org/doi/full/10.1056/NEJMoa1301675#t=article). Further work undertaken in partnership with NHS-Digital is due to be published in the BMJ this week.

Findings will also be presented at the European Society of Human Reproduction and Embryology conference.

The receipt of all data and data linkage processes have taken much longer than expected. The main benefits will be delivered once the dataset is analysed and outputs are produced.

This project has already produced the benefit of linking cohort members and their mothers, which has also enabled restricted access to more reliable identifiers of cohort members than was originally available from the HFEA. As per original data sharing agreement, these identifiers are currently being held by NHS-Digital securely, but would allow future researchers to undertake important linkage work not possible before this project (when only very limited cohort identifiers were held by the HFEA despite their mandate to collect such comprehensive data). Such future access is subject to approvals from HFEA, CAG, HRA and NHS-Digital. UCL have no access to this data.