Condition category
Pregnancy and Childbirth
Date applied
15/06/2013
Date assigned
08/08/2013
Last edited
08/12/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Both intrauterine insemination (IUI) and in vitro fertilization (IVF) are accepted treatment options for unexplained infertility. The recent National Institute for Health and Care Excellence (NICE) guideline proposes to offer IVF as a first-line treatment to these couples excluding IUI. There is no strong evidence on which this recommendation is made, so we aim to conduct this trial of IUI compared to IVF as the first-line management for unexplained infertility. If the live birth rates in both the groups are found to be same, then these couples should not be denied IUI, which is less invasive and more acceptable to patients.

Who can participate?
Couples (with female partner <37 years), trying to conceive for at least a year of unprotected intercourse, in the presence of normal semen analysis, evidence of regular ovulation, open fallopian tubes, and who had no previous fertility treatment other than clomiphene citrate will be recruited in the study.

What does the study involve?
Couples will be randomly allocated to either receive controlled ovarian hyperstimulation (COH) + IUI (50% of women) or IVF (50% of women) as the first offered treatment. The medicines used in the cycles will be the same as usual. One cycle of treatment to which the couple is allocated will be given in a 12-month period. If they are in the COH + IUI group and fail to conceive in the three cycles then they will automatically be recommended for IVF treatment outside of this study. If they are in the IVF group, then after three cycles they will not be offered IUI. This is the normal unit policy. We will compare the results in the two groups in order to see which group has a better outcome in terms of ongoing pregnancy rate/live birth rate.

What are the possible benefits and risks of participating?
The information we get from the study will help improve the treatment of people with unexplained infertility in future.
There are no added disadvantages and risks over and above the routine treatment.

Where is the study run from?
The study will be carried out in Homerton fertility unit.

When is the study starting and how long is it expected to run for?
The study started in July 2013 and will run for a year or 18 months.

Who is funding the study?
No extra funding is required for this study. Patients’ IVF treatment is usually funded by their primary care trust irrespective of their involvement in the study. No extra funding is available.

Who is the main contact?
Dr Anupa Nandi

Trial website

Contact information

Type

Scientific

Primary contact

Dr Anupa Nandi

ORCID ID

Contact details

Homerton Fertility Unit
Homerton Hospital
London
E9 6SR
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

Version no. 2.0

Study information

Scientific title

Controlled ovarian stimulation and intrauterine insemination or in vitro fertilization for the first line treatment of unexplained infertility: a randomised controlled trial

Acronym

Study hypothesis

What should be the first line treatment option for couples with unexplained infertility: intrauterine insemination (IUI) or in vitro fertilization (IVF)?

Ethics approval

Brent Ethics Committee, 28/05/2013, ref: 13/LO/0550

Study design

Single centre randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Best first line treatment options for unexplained infertility

Intervention

Randomisation will be performed by an independent worker in blocks of 10 and distributed in individual consecutively numbered opaque envelopes. Participants will be randomised into two groups:

Group 1: Controlled ovarian hyperstimulation (COH)+ IUI
In COH + IUI group the controlled ovarian hyperstimulation can be performed with daily subcutaneous injections of 75 IU FSH (Fostimon) starting from day 3-4 of menstrual cycle onwards. Dose might be altered according to the response of the patient to be decided by the attending clinician. The follicular growth is strictly monitored by transvaginal ultrasound. When at least 1-2 follicles with diameter 17-18mm is present, final oocyte maturation is induced by administration of recombinant chorionic gonadotropin (hCG) (Ovitrelle) and 24 – 36 hours later IUI would be performed. If >= 3 follicles of > 16mm develop then the cycle would be cancelled by withholding hCG and IUI and avoiding sexual intercourse due to risk of multiple pregnancies. Semen samples would be processed within one hour of ejaculation using density gradient centrifugation followed by washing with culture medium and then used for insemination. Single insemination will be done

Group 2: IVF
In IVF group women will undergo controlled ovarian hyperstimulation after down-regulation with GnRH agonist in a long protocol starting on day 2. COH is started with FSH (either Menopur or Gonal F) with dose ranging from 150 – 450 IU depending on initial AMH level decided by the attending clinician. Follicular tracking by transvaginal ultrasound will be performed. Treatment will be continued until follicles are > 18 mm. Ovulation is induced by hCG (Ovitrelle) and cumulus-oocyte complexes will be retrieved by transvaginal ultrasound guided oocyte retrieval 36 hours after hCG trigger. Embryos will be assessed daily for their morphological grading according to our laboratory's protocol until the time of transfer. Day of embryo transfer will be decided by the embryologist based on the embryo quality. One embryo will be transferred on either day 2 or 3 or 5 if one or more good quality embryos are available. If no good quality embryos are available then two embryos will be transferred. Luteal phase support will be provided with progesterone vaginal pessaries (Cyclogest). Non-transferred good quality embryos will be cryo-preserved. In case of unsuccessful cycle or early miscarriage, frozen embryos will be thawed and transferred and this will be counted as another cycle.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

The primary outcome is a singleton live birth

Secondary outcome measures

Secondary outcome measures are clinical pregnancy rate, multiple pregnancy rates. These are known from the ultrasound scans which every woman will have if they fall pregnant from the treatment.

Overall trial start date

17/06/2013

Overall trial end date

04/08/2016

Reason abandoned

Eligibility

Participant inclusion criteria

1. Couples with female partner's age between 23- 37 years
2. Diagnosed with unexplained infertility at the time of first treatment
3. Inability to conceive following a minimum of one year of unprotected intercourse
4. In the presence of normal semen analysis, proof of regular ovulatory cycles with a day 3 follicle stimulating hormone (FSH)<10IU/L
5. Two patent tubes and a normal uterine cavity on hysterosalpingography (HSG)

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

160 in each group.

Participant exclusion criteria

1. Female partner aged 37 years or more
2. People with physical disability or psychosexual problems who find difficulty in achieving vaginal intercourse
3. Couples in a same sex relationship (as these do not fall into the definition of unexplained infertility)
4. Couples where the male/female is HIV positive, as they would need specific consideration to methods of conception
5. Couples who have had no previous IUI or IVF treatment for infertility

Recruitment start date

10/08/2013

Recruitment end date

15/07/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Homerton Fertility Unit
London
E9 6SR
United Kingdom

Sponsor information

Organisation

Homerton University Hospital (UK)

Sponsor details

c/o Mr Narendra Aladangady
R&D Department
London
E9 6SR
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Hospital/treatment centre

Funder name

Patients’ IVF treatment is usually funded by their primary care trust irrespective of their involvement in the study.

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

08/12/2016: The recruitment dates have been updated from 17/06/2013 - 17/06/2014 to 10/08/2013 - 15/07/2015 and the overall trial end date has been updated from 17/06/2014 to 04/08/2016. In addition, the ethics approval date has been added.