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Trial record 11 of 23 for:    Estropipate

NATural Ovarian Stimulation (NATOS)

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ClinicalTrials.gov Identifier: NCT02892942
Recruitment Status : Active, not recruiting
First Posted : September 8, 2016
Last Update Posted : May 1, 2018
Sponsor:
Collaborator:
MerckSerono Pharmaceuticals
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Infertility Drug: Gonal-F® Drug: Cetrotide® Phase 4

Detailed Description:

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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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 129 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Innovative Controlled Ovarian Hyperstimulation (COH) Protocol That Combines Large Oocyte Availability and Physiologic Estrogenic Environment for Good Prognosis In Vitro Fertilization and Embryo Transfer (IVF-ET) Patients
Actual Study Start Date : January 13, 2017
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Control Group

Background therapy which is the usual COH treatment:

  • Recombinant FSH (Gonal-F®, 225 to 450 IU/d; MerckSerono Pharmaceuticals) from day 2 of their menstrual cycle onward,
  • GnRH antagonist (Cetrotide®, MerckSerono Pharmaceuticals) 0.25 mg/day, S.C., starting on day 6 of Gonal-F®.
Drug: Gonal-F®
225 to 450 IU/d; from day 2 of menstrual cycle onward

Drug: Cetrotide®
0.25 mg/day, starting on day 6 of Gonal-F®.

Experimental: NATOS Group

Background therapy which is the usual COH treatment:

  • Recombinant FSH (Gonal-F®, 225 to 450 IU/d; MerckSerono Pharmaceuticals) from day 2 of their menstrual cycle onward,
  • GnRH antagonist (Cetrotide®, MerckSerono Pharmaceuticals) 0.25 mg/day, S.C., starting on day 6 of Gonal-F®.

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

Drug: Gonal-F®
225 to 450 IU/d; from day 2 of menstrual cycle onward

Drug: Cetrotide®
0.25 mg/day, starting on day 6 of Gonal-F®.

Drug: Cetrotide®
1.5 mg/day (6 ampoules of 0.25 mg), starting on day 1 (S1) of Gonal-F® treatment until dhCG




Primary Outcome Measures :
  1. Live birth obtained after IVF-ET [ Time Frame: 1 month post-partum ]
    Live birth defined as delivery ≥ 22 weeks of amenorrhea


Secondary Outcome Measures :
  1. Number of oocytes obtained [ Time Frame: At oocyte retrieval (14±8 days after start of treatment) ]

Other Outcome Measures:
  1. Number of embryos obtained [ Time Frame: At day 2 of embryo development ]
  2. Clinical pregnancy [ Time Frame: 7 weeks of amenorrhea ]
    Clinical pregnancy defined as pregnancy with an US-detectable gestational sac at 7 weeks of amenorrhea

  3. Embryo implantation [ Time Frame: 7 weeks of amenorrhea ]
    Embryo implantation defined as the total number of intrauterine gestational sacs divided by the total number of embryos transferred

  4. Miscarriage [ Time Frame: Between 7 and 13 weeks of amenorrhea ]
    Miscarriage defined as a pregnancy loss between 7 and 13 weeks of amenorrhea

  5. "Top" quality embryo [ Time Frame: 4 and 5 days after hCG administration ]
    Embryo data assessed by the number of embryos with adequate morphology

  6. Blastulation [ Time Frame: 7 days after hCG administration ]
    Number of cleaving embryos having reached the blastocyst stage

  7. Adverse events occurring during COH [ Time Frame: Within the first 30 days after the start of treatment; ]
    Presence of ovarian hyperstimulation syndrome (OHSS) +/- severity is measured using OHSS evaluation scale

  8. Gestational age at delivery [ Time Frame: 1 month post-partum ]
  9. Birth weight [ Time Frame: 1 month post-partum ]
  10. Pregnancy complications [ Time Frame: 1 month post-partum ]
    antepartum haemorrhage, placental abruption, hypertensive disorders, and perinatal mortality

  11. Patient's quality of life during COH [ Time Frame: At 14 days from start of treatment with cetrotide (plus or minus 8 days) ]
    Fertiqol modified

  12. Reduced serum E2 levels on dhCG (< 800 pg/mL) [ Time Frame: the day of hCG administration ]
    serum E2 levels will be measured from each blood sample obtained during COH

  13. Serum androgens levels during COH [ Time Frame: Within the first 19 days after start of treatment with cetrotide (plus or minus 8 days) ]
    Serum androgens levels (testosterone, SHBG, androstenedione)



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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • IVF-ET candidates (excluding PGD and oocyte donor);
  • Body mass index from 18 to 30 kg/m2;
  • Non smokers;
  • Regular menstrual cycles (25-35 days);
  • Presence of both ovaries;
  • Antral follicle count (follicles measuring from 3 to 10 mm in diameter) ranging from 10 to 30 on cycle days 2 to 4;
  • Serum AMH levels ranging from 0.5 to 5.0 ng/mL;
  • Normal endometrium at ultrasound (US) and/or hysteroscopy;
  • Informed consent signed

Exclusion Criteria:

  • Iatrogenic ovarian insufficiency (surgery, radiotherapy, chemotherapy);
  • Uterine abnormalities as demonstrated by pelvic US and/or hysteroscopy;
  • Usual contra-indications for COH (cancer risk, blood coagulation disorders, etc)
  • Renal insufficiency

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02892942


Locations
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France
Hôpital Antoine Béclère
Clamart, France, 92141
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
MerckSerono Pharmaceuticals
Investigators
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Principal Investigator: RENATO FANCHIN, MD, PhD Assistance Publique - Hôpitaux de Paris

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02892942     History of Changes
Other Study ID Numbers: P150947
First Posted: September 8, 2016    Key Record Dates
Last Update Posted: May 1, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Controlled ovarian hyperstimulation
Estradiol
Embryo implantation
Endometrial receptivity
Fertility preservation
Additional relevant MeSH terms:
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Infertility
Genital Diseases, Male
Genital Diseases, Female
Cetrorelix
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists