Infertility Clinical Trial
Official title:
A Phase IV, Prospective, Observational, Open Label, Single Centre Cohort Trial to be Conducted in Norway During One Year to Assess the Cumulative Pregnancy Rate in a New Series of In-vitro Fertilization (IVF) Treatment Cycles Following Three or More Previous IVF Treatment Cycles Without Live Birth.
The primary objective of this observational study is to assess the cumulative rate of
ongoing pregnancy at 10 ±2 weeks after hCG administration in a new series of IVF-treatment
cycles in a total of 176 subjects, who have undergone three or more previous IVF-treatment
cycles without live birth. Secondary objectives include subgroup analysis on the effect of
age on the likelihood of pregnancy at 10 ±2 weeks after hCG administration in a new series
of IVF-treatment cycles in patients < 35 years and ≥ 35 years, who have undergone three or
more previous IVF-treatment cycles without live birth.
The information obtained from this trial will be helpful for subjects who are considering
further IVF treatments and for IVF centres, as well as for the formulation of governmental
policies regarding healthcare reimbursement in Norway.
Since IVF processes were established in 1978, there has been a dramatic increase in the
numbers of IVF treatment cycles performed worldwide. In 2003, the total numbers of reported
IVF cycles were 132,932 from 725 clinics in 28 European countries, 7,535 IVF/intra
cytoplasmic sperm injection (ICSI) cycles from 24 centres in Canada, and over 100,000 IVF
cycles from 399 centres in the U.S.
Of all the assisted reproductive technology (ART) procedures available, IVF leads to the
highest pregnancy rate per cycle. The degree to which governments reimburse subjects for IVF
treatment varies widely among countries in Europe and North America. In Norway, infertile
subjects are offered a maximum of three IVF-cycles reimbursed by the government. If three
cycles are unsuccessful, subjects must pay for further treatments. This policy might lead
subjects to believe that the probability of achieving pregnancy after four or more cycles is
very low and, therefore, not worth the cost or effort.
However, a number of published studies show evidence of successful outcomes for additional
IVF-cycles after three (or more) cycles with negative results. Many studies show only a
modest decline of success with repeated IVF cycles. In addition, a preliminary retrospective
analysis of the clinical pregnancy rate in subjects treated at the trial centre during 2007
showed that subjects, who underwent additional one to three IVF-treatment cycles, had a
cumulative success rate of 52% (based on clinical experience from 62 subjects at the Hausken
clinic in 2007). Thus, these studies indicate that there is a reasonable chance of achieving
a healthy pregnancy and live birth after three previous IVF-treatment failures.
In fact, age is likely to be a more important factor than the number of previous IVF
treatment failures in determining a successful outcome. Several studies have demonstrated
that older women have lower rates of conception and live births, and higher rates of
pregnancy failure.
Treatment of subfertility and infertility by ART such as IVF and embryo transfer (ET)
requires multiple follicular development to increase the number of female gametes, and the
chances of a successful treatment outcome. Ovarian stimulation in IVF/ICSI currently
includes suppression of endogenous luteinising hormone (LH) secretion by administration of a
gonadotropin releasing hormone (GnRH) analogue, followed by stimulation of multiple
follicular development by exogenous follicular stimulating hormone (FSH) administration.
When adequate follicular development is achieved, a single dose of human chorionic
gonadotropin (hCG) or LH is administered to mimic the endogenous LH surge and induce oocyte
maturation.
A total of 176 subjects who had previously undergone three or more IVF-treatment cycles that
did not result in live birth will undergo a new series of IVF-treatment cycles using Gonal-f
or Pergoveris or Gonal-f and Luveris. Subjects both < 35 years and ≥ 35 years will be
included. Subgroup analysis will take into account the effect of age on the likelihood of
success after repeated cycles of IVF. The investigators will systematically follow-up these
subjects to observe their cumulative ongoing pregnancy rate.
The study will consist of a screening period (≤-4months) during which the following trial
assessments will be made: demographics, medical history, concomitant medications, clinical
examination, vital signs, number of antral follicles and a subject diary will be handed out
to the subjects. Between screening and the beginning of treatment, there will an optional
telephone consultation during which any screening information or changes in concomitant
medications will be updated. Down-regulation treatment will start within 3 months following
the screening visit during the pre treatment period with GnRH daily agonist or antagonist
commercially available in Norway, for pituitary gonadotrope cell desensitisation. FSH
treatment will begin by administering either Gonal-f or Pergoveris or Gonal-f and Luveris
after at least 2 weeks of GnRH agonist down-regulation. If a GnRH antagonist protocol is
used, FSH injections will start on Day 2 of the menstrual cycle.
Follicular development will be monitored according to the centre's standard practice by
ultrasound and/or estradiol (E2) levels, until the protocol hCG requirement is met (i.e. at
least 1 follicle ≥18 mm and 2 follicles ≥16 mm) at which time the subject will receive hCG
(Day 0), according to the routine practice of the centre, in order to induce final oocyte
maturation. Ovum Pick Up (Day 2), IVF, ET (Day 4-7) and luteal phase support will be
performed as per the centre's standard practice. During the treatment period several
assessments will be made and any adverse events (AEs) observed during the trial will be
recorded. A urine pregnancy test will be performed 16 days post hCG administration. In case
of negative urine pregnancy test, the subject will be assessed for the post-treatment safety
follow-up and the cycle will be considered as 'completed'. The post-treatment safety
follow-up can take place simultaneously with the next cycle's screenings visit. If subject
drops out, the early termination visit will replace the post-treatment safety follow-up. If
the urine pregnancy test is positive, clinical and later ongoing pregnancy will be
subsequently confirmed by ultrasound scan according to the centre's routine practice. At
this last visit, all subjects will be assessed for the post-treatment safety follow-up and
will be considered 'completed'. Pregnancy outcome in pregnant subjects will be optionally
followed up until delivery.
Adverse events and serious adverse events (SAEs) will be assessed if spontaneously reported
by the subjects at all study visits: during an optional telephone consultation between
screening and the beginning of treatment, ultrasound scan (Day -7-0), OPU (Day 2), telephone
consultation (Day 3), embryo transfer (Day 4-7), telephone consultation (Day 16), scan week
12 (assessed 10 weeks after hCG administration), post-treatment safety follow-up, 1-Year
follow-up, and at early termination (if applicable).
;
Observational Model: Cohort, Time Perspective: Prospective
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT03607409 -
Role of Inhibin A as Biomarker for Ovarian Response for IVF Treatment
|
||
Recruiting |
NCT02312076 -
GnRHa for Luteal Phase Support in Long GnRHa Protocol Cycles
|
Phase 4 | |
Terminated |
NCT02161861 -
Improvement of IVF Fertilization Rates, by the Cyclic Tripeptide FEE - Prospective Randomized Study
|
N/A | |
Completed |
NCT03287479 -
Comparison of a Semi-automated Closed Vitrification System (Gavi®) With a Manual Open Vitrification Sytem (Cryotop®)
|
N/A | |
Terminated |
NCT03522350 -
Randomized Trial Comparing EmbryoScope With EmbryoScope+.
|
N/A | |
Completed |
NCT04496284 -
Embryo Transfer Outcomes After Vitrification With Slush Nitrogen Compared to Liquid Nitrogen
|
N/A | |
Completed |
NCT03623659 -
pArtiaL zonA pelluciDa Removal by assisteD hatchINg of Blastocysts
|
N/A | |
Completed |
NCT03895099 -
New Ovarian Stimulation With Random Start, Use of Progestin Protocol for Oocyte Donors
|
Phase 3 | |
Active, not recruiting |
NCT04142112 -
Randomized, Standard-Controlled, Study to Evaluate the Ohana IVF Sperm Preparation Kit, SPeRtility IVF Next Generation
|
N/A | |
Completed |
NCT03152643 -
Cumulative Live Birth Rates After Cleavage-stage Versus Blastocyst-stage Embryo Transfer
|
N/A | |
Recruiting |
NCT03683771 -
Assessment of Endometrial Pattern and Sub-endometrial Vascularity in ICSI Outcome
|
||
Recruiting |
NCT03161119 -
Comparing Two Different Embryo Transfer Catheters
|
N/A | |
Completed |
NCT04108039 -
Micronized Progesterone vs Gonadotropin-releasing Hormone (GnRH) Antagonist in Freeze-all IVF Cycles.
|
N/A | |
Completed |
NCT03677492 -
Supplementing Intracytoplasmic Sperm Injection Handling Medium With Cytochalasin D ( ICSI-CD)
|
N/A | |
Completed |
NCT03678584 -
Supplementing Intracytoplasmic Sperm Injection Handling Medium With Chaetoglobosin A ( ICSI-CA)
|
N/A | |
Completed |
NCT03678558 -
Oocyte Vitrification Aided With Cytochalasin B
|
N/A | |
Completed |
NCT03678818 -
Supplementing Intracytoplasmic Sperm Injection Handling Medium With Latrunculin A (ICSI-LA)
|
N/A | |
Completed |
NCT03678571 -
Oocyte Vitrification Aided With Latrunculin A
|
N/A | |
Completed |
NCT03678597 -
Supplementing Intracytoplasmic Sperm Injection Handling Medium With Latrunculin B ( ICSI-LB)
|
N/A | |
Completed |
NCT03678610 -
Handling Medium for ICSI With Ionomycin and Latrunculin A
|
N/A |