NATural Ovarian Stimulation

Infertility Clinical Trial

— NATOS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02892942
• Other study ID #: P150947
• Status: Completed
• Phase: Phase 4
• Start date: January 13, 2017
• Est. completion date: February 8, 2019

Study information

• Verified date: April 2021
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 129
• Est. completion date: February 8, 2019
• Est. primary completion date: February 8, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Infertility

Intervention

Drug:
• Gonal-F®
225 to 450 IU/d; from day 2 of menstrual cycle onward
• Cetrotide®
0.25 mg/day, starting on day 6 of Gonal-F®.
• Cetrotide®
1.5 mg/day (6 ampoules of 0.25 mg), starting on day 1 (S1) of Gonal-F® treatment until dhCG

Locations

Country	Name	City	State
France	Hôpital Antoine Béclère	Clamart

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	MerckSerono Pharmaceuticals

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of embryos obtained		At day 2 of embryo development
Other	Clinical pregnancy	Clinical pregnancy defined as pregnancy with an US-detectable gestational sac at 7 weeks of amenorrhea	7 weeks of amenorrhea
Other	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
Other	Miscarriage	Miscarriage defined as a pregnancy loss between 7 and 13 weeks of amenorrhea	Between 7 and 13 weeks of amenorrhea
Other	"Top" quality embryo	Embryo data assessed by the number of embryos with adequate morphology	4 and 5 days after hCG administration
Other	Blastulation	Number of cleaving embryos having reached the blastocyst stage	7 days after hCG administration
Other	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;
Other	Gestational age at delivery		1 month post-partum
Other	Birth weight		1 month post-partum
Other	Pregnancy complications	antepartum haemorrhage, placental abruption, hypertensive disorders, and perinatal mortality	1 month post-partum
Other	Patient's quality of life during COH	Fertiqol modified	At 14 days from start of treatment with cetrotide (plus or minus 8 days)
Other	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
Other	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)
Primary	Live birth obtained after IVF-ET	Live birth defined as delivery = 22 weeks of amenorrhea	1 month post-partum
Secondary	Number of oocytes obtained		At oocyte retrieval (14±8 days after start of treatment)