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| Name | Class |
|---|---|
| MerckSerono Pharmaceuticals | UNKNOWN |
| URC-CIC Paris Descartes Necker Cochin | OTHER |
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To overcome unsuitable effects of controlled ovarian hyperstimulation (COH )while maintaining large oocyte availability, investigators elaborated an innovative protocol (NATural Ovarian Stimulation) that dissociates E2 production from multiple follicle development.
The purpose of this prospective, randomized trial is to demonstrate that, in a good prognosis IVF-ET population, the physiological E2 environment resulting from NATOS significantly improves IVF-ET outcome when compared to the conventional GnRH antagonist protocol.
Controlled ovarian hyperstimulation (COH) seeks to improve IVF-ET results by increasing per-cycle oocyte and embryo availability. Yet, the coexistence of multiple preovulatory follicles engenders compulsory alterations in the endocrine milieu of the follicular phase. The most evident of them are the extremely high serum estradiol (E2) levels. The 10 to 15-fold increase in E2 levels as a result of COH has been shown to provoke unwanted consequences in both embryo quality and uterine receptivity.
Therefore, investigators elaborated an innovative COH protocol (NATural Ovarian Stimulation) that aimed at dissociating E2 production from multiple follicle development. To obtain this effect, they virtually curtailed endogenous LH production by using GnRH antagonist doses as strong and frequent enough to maintain E2 levels around the physiological range during standard exogenous FSH-only administration. Given that high E2 levels are commonly reached in patients having a normal follicle endowment, NATOS should target this group of good prognosis IVF-ET candidates. Indeed, this new COH approach was first tested in a pilot study that included 15 good prognosis IVF-ET candidates, aged 25-35 years, who volunteered to undergo NATOS. 11 out of 15 patients achieved a pregnancy. These pilot results spurred them to conduct a prospective, randomized trial to demonstrate that, in a good prognosis IVF-ET population, the physiological E2 environment resulting from NATOS significantly improves IVF-ET outcome when compared to the conventional GnRH antagonist protocol.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control Group | Active Comparator | Background therapy which is the usual COH treatment:
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| NATOS Group | Experimental | Background therapy which is the usual COH treatment:
GnRH antagonist treatment (Cetrotide®, MerckSerono Pharmaceuticals) will be reinforced and patients will receive 1.5 mg/day (6 ampoules of 0.25 mg), S.C., starting on day 1 (S1) of Gonal-F® treatment until dhCG |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Gonal-F® | Drug | 225 to 450 IU/d; from day 2 of menstrual cycle onward |
|
| Measure | Description | Time Frame |
|---|---|---|
| Live birth obtained after IVF-ET | Live birth defined as delivery ≥ 22 weeks of amenorrhea | 1 month post-partum |
| Measure | Description | Time Frame |
|---|---|---|
| Number of oocytes obtained | At oocyte retrieval (14±8 days after start of treatment) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of embryos obtained | At day 2 of embryo development | |
| Clinical pregnancy | Clinical pregnancy defined as pregnancy with an US-detectable gestational sac at 7 weeks of amenorrhea | 7 weeks of amenorrhea |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| RENATO FANCHIN, MD, PhD | Assistance Publique - Hôpitaux de Paris | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hôpital Antoine Béclère | Clamart | 92141 | France |
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| ID | Term |
|---|---|
| D007246 | Infertility |
| ID | Term |
|---|---|
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| C571801 | follitropin alfa |
| C062876 | cetrorelix |
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| Cetrotide® | Drug | 0.25 mg/day, starting on day 6 of Gonal-F®. |
|
| Cetrotide® | Drug | 1.5 mg/day (6 ampoules of 0.25 mg), starting on day 1 (S1) of Gonal-F® treatment until dhCG |
|
| Embryo implantation | Embryo implantation defined as the total number of intrauterine gestational sacs divided by the total number of embryos transferred | 7 weeks of amenorrhea |
| Miscarriage | Miscarriage defined as a pregnancy loss between 7 and 13 weeks of amenorrhea | Between 7 and 13 weeks of amenorrhea |
| "Top" quality embryo | Embryo data assessed by the number of embryos with adequate morphology | 4 and 5 days after hCG administration |
| Blastulation | Number of cleaving embryos having reached the blastocyst stage | 7 days after hCG administration |
| Adverse events occurring during COH | Presence of ovarian hyperstimulation syndrome (OHSS) +/- severity is measured using OHSS evaluation scale | Within the first 30 days after the start of treatment; |
| Gestational age at delivery | 1 month post-partum |
| Birth weight | 1 month post-partum |
| Pregnancy complications | antepartum haemorrhage, placental abruption, hypertensive disorders, and perinatal mortality | 1 month post-partum |
| Patient's quality of life during COH | Fertiqol modified | At 14 days from start of treatment with cetrotide (plus or minus 8 days) |
| Reduced serum E2 levels on dhCG (< 800 pg/mL) | serum E2 levels will be measured from each blood sample obtained during COH | the day of hCG administration |
| Serum androgens levels during COH | Serum androgens levels (testosterone, SHBG, androstenedione) | Within the first 19 days after start of treatment with cetrotide (plus or minus 8 days) |