ANZCTR - Registration

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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]

None

Universal Trial Number (UTN)

U1111-1194-0931

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Adenomyosis

Infertility

Condition category

Condition code

Reproductive Health and Childbirth

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]

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]

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]

9 months following embryo transfer.

Secondary outcome [1]

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]

1 month following stimulation cycle

Secondary outcome [2]

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]

3 months following embryo transfer.

Secondary outcome [3]

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]

9 months following embryo transfer.

Secondary outcome [4]

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]

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]

Monash IVF - Hawthorn - Hawthorn

Recruitment hospital [2]

Monash IVF - Clayton - Clayton

Recruitment hospital [3]

Monash IVF Geelong - Geelong

Recruitment postcode(s) [1]

3122 - Hawthorn

Recruitment postcode(s) [2]

3168 - Clayton

Recruitment postcode(s) [3]

3220 - Geelong

Recruitment postcode(s) [4]

3121 - Richmond

Funding & Sponsors

Funding source category [1]

Self funded/Unfunded

Name [1]

Dr Hugo Fernandes

Address [1]

Suite 9.4, Level 9
89 Bridge Road
Richmond VIC 3121

Country [1]

Australia

Funding source category [2]

Commercial sector/Industry

Name [2]

Monash IVF

Address [2]

Pelaco Building 1
Level 1,
21-31 Goodwood Street
Richmond VIC 3121

Country [2]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Not required

Ethics committee name [1]

Ethics committee address [1]

Ethics committee country [1]

Date submitted for ethics approval [1]

Approval date [1]

Ethics approval number [1]

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

Dr Hugo Fernandes

Address

Monash IVF
Suite 9.4, Level 9
Epworth Hospital
89 Bridge Road
Richmond VIC 3121

Country

Australia

Phone

+61 03 9516 2895

Fax

+61 03 9421 5932

[email protected]

Contact person for public queries

Name

Hugo Fernandes

Address

Monash IVF
Suite 9.4, Level 9
Epworth Hospital
89 Bridge Road
Richmond VIC 3121

Country

Australia

Phone

+61 03 9516 2895

Fax

+61 03 9421 5932

[email protected]

Contact person for scientific queries

Name

Hugo Fernandes

Address

Monash IVF
Suite 9.4, Level 9
Epworth Hospital
89 Bridge Road
Richmond VIC 3121

Country

Australia

Phone

+61 03 9516 2895

Fax

+61 03 9421 5932

[email protected]

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

Source	Title	Year of Publication	DOI
Embase	The impact of adenomyosis on IVF outcomes: A prospective cohort study.	2021	https://dx.doi.org/10.1093/hropen/hoab015

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically