Infertility, Poor Ovarian Response
Conditions
Brief summary
In combination with the existing literature, previous work indicates that 1) women with poor ovarian response fulfilling the Bologna criteria have very low pregnancy rates, irrespective of age 2) current treatment protocols demonstrate ongoing pregnancy rates that do not exceed 8.5% and 3) corifollitropin alfa followed by hpHMG might increase ongoing pregnancy rates in young patients (\<40years old) fulfilling the criteria. These findings provide a strong rationale for a definitive large RCT. The COMPORT study will provide conclusive evidence regarding the superiority or not of this novel protocol with corifollitropin alfa followed by hpHMG for the treatment of young poor ovarian responders fulfilling the Bologna criteria.
Detailed description
Recently, the European Society of Human Reproduction and Embryology developed a new definition in order to select patients suitable for inclusion in future clinical trials as poor ovarian responders, the so-called Bologna criteria. However, a limited number of studies has been published to date including patients with poor ovarian response according to the Bologna criteria, whereas no randomized trial is published or ongoing for this population. Preliminary reports in Bologna poor responders highlight the limited prospects for these women. Natural cycle IVF has been shown to result in disappointingly low live birth rates, regardless of patients' age and ovarian stimulation with widely accepted treatment modalities, e.g. short agonist protocol, did not appear demonstrate substantial benefits. Nonetheless, despite the disappointing results from the vast majority of the preliminary studies in this population, a recent pilot study by our group has shown that a specific protocol may indeed be a promising option for women of younger age fulfilling the Bologna criteria. Corifollitropin alfa followed by highly purified hMG in an antagonist protocol demonstrated an ongoing pregnancy rate of 28% in women \<40years, strongly suggesting the conduction of a future randomized trial testing this novel treatment protocol
Interventions
DRUGCorifollitropin alfa
Corifollitropin alfa 150μg on day 2 of the menstrual cycle (stimulation day 1)
DRUGrecombinant FSH
recombinant FSH 300IU/daily from day 2 of the cycle (stimulation day 8)until day of ovulation triggering
DRUGGanirelix
Ganirelix 0.25mg/daily from day 7 of the cycle(stimulation day 6) until day of ovulation triggering
DRUGhp HMG
hp HMG 300IU/daily from day 9 of the cycle (stimulation day 8)until day of ovulation triggering
Sponsors
University of Medicine and Pharmacy at Ho Chi Minh City
Universitair Ziekenhuis Brussel
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 39 Years
Healthy volunteers
No
Inclusion criteria
* Age less than 40 years * Fulfillment of the Bologna criteria for poor ovarian response. Based on inclusion criteria two patients' categories are eligible: 1. Women \< 40 years old AND ≤3 oocytes in one of the previous cycles AND (Antral follicle count \<7 or antimullerian hormone serum values \<1.1 ng/ml) 2. Women \<40 years old and ≤3 oocytes in two the previous cycles with maximum ovarian stimulation In addition women less than 40 years old will be considered eligible if they had undergone previous ovarian surgery or chemotherapy (risk factors for poor ovarian response) and have an AMH\<1.1ng/ml or an AFC\<7, as suggested by the Bologna criteria
Exclusion criteria
* Uterine abnormalities * Recent history of any current untreated endocrine abnormality * Unilateral or bilateral hydrosalpinx (visible on transvaginal ultrasound, unless clipped) * Contraindications for the use of gonadotropins * Recent history of severe disease requiring regular treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ongoing pregnancy | 9-10 weeks of gestation | The presence of intrauterine gestational sac with an embryonic pole demonstrating cardiac activity at 9-10 weeks of gestation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical pregnancy | 7 weeks of gestation | The presence of intrauterine gestational sac at 7 weeks of gestation |
| Biochemical pregnancy | 2 weeks after embryo transfer | Positive pregnancy test 2 weeks after embryo transfer |
| Number of oocytes retrieved | 9 -20 days from initiation of ovarian stimulation | The outcome will be evaluated on the day of oocyte retrieval |
Other
| Measure | Time frame | Description |
|---|---|---|
| Endocrine parameters (LH,FSH, E2, Progesterone) during ovarian stimulation | Days 1,6,8,10 of stimulation and day of ovulation triggering | — |
| Cycle cancellation due to poor ovarian response | Day 8-10 of ovarian stimulation | Number of cycles cancelled due to monofollicular or no follicular development |
| Cycle cancellation due to serious adverse effects of medication | 20-25 days after initiation of stimulation | 20-25 days after the initiation of ovarian stimulation all patients (cycles) will be monitored for the occurence of any adverse effect and cycle cancellation(during ovarian stimulation) due to a serious adverse effect from medication |
| Number of cycles reaching the stage of embryo transfer | 9 -20 days from initiation of ovarian stimulation | The outcome will be evaluated 3 days after oocyte retrieval |
| Number and quality of embryos | Day of embryo transfer | 3 days after oocyte retrieval |
| Number of cycles with frozen supernumerary embryos | 9 -20 days from initiation of ovarian stimulation | The outcome will be evaluated 5 days after oocyte retrieval or 2-3 days after embryo transfer in case of an embryo transfer |
Countries
Belgium, Vietnam
Outcome results
None listed