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Trial registered on ANZCTR


Registration number
ACTRN12617000796381
Ethics application status
Not required
Date submitted
22/03/2017
Date registered
31/05/2017
Date last updated
3/05/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Effect of Adenomyosis on In Vitro Fertilisation - Embryo Transfer (IVF-ET) outcomes.
Scientific title
The effect of sonographically diagnosed adenomyosis on the outcome of In Vitro Fertilisation-Embryo Transfer.
Secondary ID [1] 291416 0
None
Universal Trial Number (UTN)
U1111-1194-0931
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Adenomyosis 302431 0
Infertility 302432 0
Condition category
Condition code
Reproductive Health and Childbirth 302001 302001 0 0
Fertility including in vitro fertilisation

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Adenomyosis is a condition characterised by the presence of heterotopic endometrial glands and stroma in the myometrium with surrounding myometrial hyperplasia. Patients undergoing fertility treatment at Monash IVF all have baseline pelvic ultrasound scan. Patients with Adenomyosis will be identified by ultrasound criteria including a combination of:
Uterine enlargement in the absence of leiomyomas.
Asymmetric enlargement of the anterior or posterior myometrial wall.
Lack of contour abnormality or mass effect.
Heterogeneous, poorly circumcised areas within the myometrium.
Hyperechoic islands or nodules, finger-like projections or linear striations.
Anechoic lacunae or cysts of varying size.
Increased echo texture of the myometrium.

All patients will undergo a stimulated fertility cycle and invitro-fertilisiation/embryo transfer (IVF ET) at Monash IVF. The type of fertility cycle will be determined by the patients treating clinician and may be GnRH agonist or GnRH antagonist based, but all cycles must involve an embryo transfer.

Following each embryo transfer (ET), patients will be followed for a maximum of 9 months.
Intervention code [1] 297451 0
Diagnosis / Prognosis
Comparator / control treatment
The control group are those patients undergoing fertility treatment at Monash IVF who have a baseline pelvic ultrasound scan that does not have features to suggest the presence of Adenomyosis.
Control group
Active

Outcomes
Primary outcome [1] 301426 0
Live birth rate per IVF-ET cycle in adenomyosis versus no adenomyosis group.

Initial assessment is at 2 weeks folloeing ET with a serum bHCG test to determine whether a biochemical pregnancy exists. An ultrasound at 6-7 weeks post ET will confirm a live pregnancy. Live birth will be assessed as they occur or at 9 months.

The primary outcome data is routinely collected by our unit as part of mandatory self reporting of results to the Victorian Assisted Reproductive Treatment Authority (VARTA). The initial blood test and US is usually done in house and is available from our pathology/radiology provider. The other outcomes are followed up at the appropriate time by each patients nurse by contacting the patient directly.
Timepoint [1] 301426 0
9 months following embryo transfer.
Secondary outcome [1] 332603 0
Utilisation rate (Number of embryos transferred + Number Frozen/Total oocytes fertilised) per stimulation in adenomyosis versus no adenomyosis group.

The resulst used to assess this outcome are routinely collected by our unit as part of mandatory self-auditing to comply with Victorian Assisted Reproductive Treatment Authority (VARTA). The location, quality, quantity and outcome of every embryo and egg managed by our unit is strictly controlled. All data exists on our patient management system.
Timepoint [1] 332603 0
1 month following stimulation cycle
Secondary outcome [2] 332604 0
Clinical pregnancy rate per IVF-ET cycle in adenomyosis versus no adenomyosis group.

A clinical pregnancy is defined as a pregnancy that is located within the intrauterine cavity and proven to have a fetal heart been as seen on US. This US can occur at any time after 6 weeks gestation. This data is routinely collected by our unit as part of mandatory self reporting of results to the Victorian Assisted Reproductive Treatment Authority (VARTA). The other outcomes are followed up at the appropriate time by each patients nurse by contacting the patient directly.
Timepoint [2] 332604 0
3 months following embryo transfer.
Secondary outcome [3] 332605 0
Miscarriage rate per pregnancy in adenomyosis versus no adenomyosis group.

A miscarriage is any clinical pregnancy that is proven to have a fetal heart been as seen on US that does not continue on to a live birth. This data is routinely collected by our unit. The unit becomes aware of miscarriages by treating doctors informing the unit, by patients representing for further IVF treatment or by follow up by each patients nurse by contacting the patient directly.
Timepoint [3] 332605 0
9 months following embryo transfer.
Secondary outcome [4] 335327 0
Ectopic pregnancy rate per pregnancy in adenomyosis versus no adenomyosis group.

An ectopic pregnancy is any clinical pregnancy that is not found to exist wholly within the uterine cavity. This data is routinely collected by our unit. The unit becomes aware of ectopics by treating doctors informing the unit, by patients representing for further IVF treatment or by follow up by each patients nurse by contacting the patient directly.
Timepoint [4] 335327 0
9 months following embryo transfer.

Eligibility
Key inclusion criteria
All women treated for infertility by Monash IVF over the next 2 years who:
1. Are aged 18 – 45
2. Are on their first egg collection cycle
3. Have a fresh ET on Day 5 following a down regulation or antagonist cycle
4. Have an US study at Monash Ultrasound for Women within 6 months of IVF-ET (Baseline US)
5. Have any cause of infertility
6. Have complete study data on Monash IVF database (up to birth if pregnant)
7. Used their own eggs


Adenomyosis as diagnosed on ultrasound by a tertiary level COGU or board certified Obstetrician and Gynaecologist using their normal US technique and having findings of any of:
1. Uterine enlargement in the absence of leiomyomas
2. Asymmetric enlargement of the anterior or posterior myometrial wall
3. Lack of contour abnormality or mass effect
4. Heterogeneous, poorly circumcised areas within the myometrium
5. Hyperechoic islands or nodules, finger-like projections or linear striations
6. Anechoic lacunae or cysts of varying size
7. Increased echo texture of the myometrium


Cause of Infertility:
1. Male factor
2. Endometriosis
3. Ovulation disorder
4. Tubal factor
5. Unexplained
5a. All cases not able to be accommodated in other group.
Minimum age
18 Years
Maximum age
45 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Not within the inclusion criteria.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
On average, IVF pregnancy rates for a day 5 fresh cycle is estimated at 30%. Sample size calculation for a 10% reduction from a 30% clinical pregnancy rate (power 80% & alpha 0.05) with a 3:1 patient ratio requires 640 patients with no adenomyosis and 220 with adenomyosis.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
1/01/2016
Date of last participant enrolment
Anticipated
30/09/2018
Actual
Date of last data collection
Anticipated
30/09/2018
Actual
Sample size
Target
860
Accrual to date
770
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 7716 0
Monash IVF - Hawthorn - Hawthorn
Recruitment hospital [2] 7717 0
Monash IVF - Clayton - Clayton
Recruitment hospital [3] 7718 0
Monash IVF Geelong - Geelong
Recruitment postcode(s) [1] 15641 0
3121 - Richmond
Recruitment postcode(s) [2] 15563 0
3122 - Hawthorn
Recruitment postcode(s) [3] 15639 0
3168 - Clayton
Recruitment postcode(s) [4] 15640 0
3220 - Geelong

Funding & Sponsors
Funding source category [1] 295885 0
Self funded/Unfunded
Name [1] 295885 0
Dr Hugo Fernandes
Country [1] 295885 0
Australia
Funding source category [2] 296597 0
Commercial sector/Industry
Name [2] 296597 0
Monash IVF
Country [2] 296597 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Monash IVF
Address
Pelaco Building 1
Level 1,
21-31 Goodwood Street
Richmond VIC 3121
Country
Australia
Secondary sponsor category [1] 294754 0
None
Name [1] 294754 0
Address [1] 294754 0
Country [1] 294754 0

Ethics approval
Ethics application status
Not required
Ethics committee name [1] 297164 0
Ethics committee address [1] 297164 0
Ethics committee country [1] 297164 0
Date submitted for ethics approval [1] 297164 0
Approval date [1] 297164 0
Ethics approval number [1] 297164 0

Summary
Brief summary
Adenomyosis is a condition characterised by the presence of endometrial lining/glands and stroma in the muscle wall of the uterus with surrounding swelling. Typically patients present clinically with a combination of abnormal uterine bleeding, secondary period pain and a tender enlarged uterus in the fourth and fifth decades of life. Infertility is a less common presentation, however as many women are delaying having children into their late thirties and fourties, adenomyosis is increasingly encountered during the clinical work up of infertile women. A definitive link between adenomyosis and infertility has not been established, however several studies have demonstrated a strong association between the two. A recent study looking at uterine wall thickness found that in vitro fertilisation and embryo transfer (IVF-ET) outcomes decreased with increasing uterine wall thickness and findings suggestive of adenomyosis, however two small trials of IVF-ET in patients with adenomyosis found no difference in pregnancy outcomes compared to matched cases. , There is therefore limited and conflicting evidence for the effectiveness of IVF-ET in patients with adenomyosis.

The aim of this trial is to evaluate the outcomes of IVF-ET (InVitro Fertilisation - Embryo Transfer) in patients with an ultrasound diagnosis of adenomyosis.

The primary hypotheses are that:
1. IVF-ET success rates (clinical pregnancy & live-births) will be different in women with adenomyosis compared to those without adenomyosis based on ultrasound.
2. That the above finding will be true regardless of whether adenomyosis is the only cause or one of multiple causes of infertility in the female.

The secondary hypotheses are that:
1. The presence of adenomyosis will be associated with altered
1a. Implantation rates.
1b. Miscarriage rates per clinical pregnancy.
1c. Ectopic pregnancy rates per clinical pregnancy.
Trial website
Trial related presentations / publications
Public notes
This study was presented to our relevant ethics committee for evaluation. It was determined by them that as the data that is being used at all points within our study is already routinely collected from patients AND there was no intervention or alteration to the patients treatment, then this study was considered an audit of practice. Further, when patients are treated by our unit, their signed contract states that treatment and outcome data is collected as part of a mandatory reporting requirement of VARTA, but also to be used in an unidentified manner for audit and research.

Contacts
Principal investigator
Name 73198 0
Dr Hugo Fernandes
Address 73198 0
Monash IVF
Suite 9.4, Level 9
Epworth Hospital
89 Bridge Road
Richmond VIC 3121
Country 73198 0
Australia
Phone 73198 0
+61 03 9516 2895
Fax 73198 0
+61 03 9421 5932
Email 73198 0
research@drhugo.com.au
Contact person for public queries
Name 73199 0
Dr Hugo Fernandes
Address 73199 0
Monash IVF
Suite 9.4, Level 9
Epworth Hospital
89 Bridge Road
Richmond VIC 3121
Country 73199 0
Australia
Phone 73199 0
+61 03 9516 2895
Fax 73199 0
+61 03 9421 5932
Email 73199 0
research@drhugo.com.au
Contact person for scientific queries
Name 73200 0
Dr Hugo Fernandes
Address 73200 0
Monash IVF
Suite 9.4, Level 9
Epworth Hospital
89 Bridge Road
Richmond VIC 3121
Country 73200 0
Australia
Phone 73200 0
+61 03 9516 2895
Fax 73200 0
+61 03 9421 5932
Email 73200 0
research@drhugo.com.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseThe impact of adenomyosis on IVF outcomes: A prospective cohort study.2021https://dx.doi.org/10.1093/hropen/hoab015
N.B. These documents automatically identified may not have been verified by the study sponsor.