None listed
Conditions
Brief summary
The FIIX study is a randomised controlled trial that will be carried out across NZ involving couples with unexplained infertility who are eligible for public funding. They will receive either four intrauterine insemination (IUI) cycles (washed sperm placed into the uterus) or one in vitro fertilisation (IVF) cycle (embryos made in the laboratory by mixing eggs with sperm) to determine if the treatments have similar live birth rates (LBR). The trial will continue to completion of public treatment for these couple (which is two IVF cycles) and compare LBR and cost at the end. Our hypothesis is that for couples with unexplained infertility, (1) four cycles of IUI is comparable to one completed cycle of IVF for CLBR and is more cost effective; and (2) four cycles of IUI followed by two cycles of IVF will result in more live births at lower total cost than two cycles of IVF alone.
Interventions
Intrauterine insemination (IUI) followed by in vitro fertilisation (IVF) arm
Participants randomised to this arm will receive four cycles of IUI, followed by two completed cycles of IVF until pregnancy leading to live birth is achieved.
IUI treatment will begin at the start of the next menstrual cycle (day 1) following randomisation. IUI with oral ovarian stimulation will be given with five days of either oral clomiphene citrate (CC) or letrozole from cycle day 2-6. The clinicians and fertility
Intrauterine insemination (IUI) followed by in vitro fertilisation (IVF) arm Participants randomised to this arm will receive four cycles of IUI, followed by two completed cycles of IVF until pregnancy leading to live birth is achieved. IUI treatment will begin at the start of the next menstrual cycle (day 1) following randomisation. IUI with oral ovarian stimulation will be given with five days of either oral clomiphene citrate (CC) or letrozole from cycle day 2-6. The clinicians and fertility clinics involved will determine the medication used and dose as per their normal clinic policy. The dose of Clomiphene is usually between 25mg-150mg daily and letrozole 2.5-7.5mg daily. Blood tests will be taken, and monitoring for follicular development via transvaginal ultrasound will occur, according to clinic protocol, this usually will not be more than 2-3 times per cycle. On the day of ovulation semen will be washed and prepared and then directly inserted with a catheter into the cervix. The IUI procedure will be carried out either by a fertility clinic nurse trained in IUI or by the study co-ordinator (myself) a fertility subspecialty trainee. It will be carried out at the fertility clinics involved in the study. If four cycles of IUI are carried out and do not lead to live birth then the patient progresses to IVF treatment. The number of cancelled and complete cycles of IUI that have been carried out, and over what time period, will be monitored by our Data Safety Monitoring Board (DSMB) and reported back to the trial steering committee if there are concerns. Four cycles of IUI would be expected to be complete within the primary endpoint (six/seven months from the date of randomisation). IVF will be carried out by doctors, embryologists and nurses at the involved clinics in the standard way the clinic normal carries out an IVF cycle. The study is pragmatic in that the clinic and practitioner has autonomy over the cycle type, medication dose and follow up/progress regimen. Two completed cycles of IVF will be offered until a live birth is achieved. A completed cycle includes transfer of all available frozen embryos in subsequent cycles, using a single embryo transfer policy. All frozen embryos must be transferred prior to progressing into the second IVF cycle. The two IVF cycles would be expected to be complete within a 12/13 month time frame.
Sponsors
University of Auckland
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 54 Years
Healthy volunteers
No
Inclusion criteria
Inclusion criteria 1. Eligible for two packages of publicly funded fertility treatment in NZ and all of the following: a. Age - Female <39 years 4 months and male <54 years and 4months at the time of randomisation. b. Body mass index (BMI) - Female - BMI < /= 32. c. Both partners are non-smokers for three months. d. Both partners with no history of illicit drug use or alcohol abuse within the preceding 12 months. e. Day 2 FSH <15IU for the female partner f. Both partners must be a NZ citizen or resident, hold a NZ work visa or student visa which allows them to stay in NZ continuously for two years or more, or be an Australian citizen or resident who can prove intention to stay in NZ for two years or more. g. Couples must have: i. No previous children from public fertility treatment. ii. No more than one child (including adopted children) of any age to the same relationship, or iii. No more than one child from a previous relationship living at home (at least half of the time) 2. Female partner has a regular ovulatory cycle (21-35 days). 3. Female partner has evidence of patent fallopian tube(s) on hysterosalpingogram or at laparoscopy or recent intrauterine miscarriage (within 24 months) (tubal spasm is not considered tubal blockage). 4. Male partner has a total motile sperm count (TMSC) > 10 million, on last semen analysis or within two of the past three semen analyses.
Exclusion criteria
1. Women with a history of stage 3 and 4 endometriosis 2. Women with submucosal fibroids or any fibroid >8cm or fibroids between 5-8cm if endometrial cavity is distorted or cavity length is >10cm. 3. Couple who require egg or sperm donation 4. Women with a past history of ectopic pregnancy or bilateral blocked tubes or tubal surgery for adhesions/hydrosalpinges.
Outcome results
None listed