Clinical trial NCT02946684: Effect of Addition of Aromatase Inhibitor to Ovarian Stimulation Therapy in IVF Treatment
Official title: Reducing the Impact of Ovarian Stimulation - The RIOT Project. Study RIOT-A: The Role of Aromatase Inhibitor in Reducing the Detrimental Effects of Ovarian Stimulation to Optimize Outcomes in Fresh Embryo Transfer Cycles
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Infertility
Lead sponsor: Herlev Hospital
Sponsor class: OTHER
Collaborators: name: Rigshospitalet, Denmark
name: Hvidovre University Hospital
name: Holbaek Sygehus
name: Region Capital Denmark
name: Copenhagen University Hospital, Denmark
name: Zealand University Hospital
First posted: 2016-10-27
Enrollment: 129
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This project seeks to determine whether estradiol suppression achieved with adjuvant treatment with an aromatase inhibitor improves end-follicular and midluteal phase parameters during IVF. 128 patients will be randomized to either placebo or active treatment.

Detailed description: The aim of the study is to investigate whether the detrimental effects of ovarian stimulation on outcomes in fresh embryo transfer cycles be ameliorated by co-treatment with aromatase inhibitors? The research questions are:

1. Can the impact of ovarian stimulation on late follicular phase sex steroid levels (and hence endometrial receptivity) be mitigated by co-treatment with aromatase inhibitors during ovarian stimulation?
2. Does co-treatment with aromatase inhibitors 'normalize' the endocrinology of the midluteal phase

Eligibility criteria: INCLUSION CRITERIA

* Indication for IVF/ICSI treatment
* Eligible for IVF/ICSI treatment according to local criteria
* Regular cycles 21-35 days (both included)
* Age \< 40
* AMH 8- 32 (both included)
* Written consent

EXCLUSION CRITERIA

* Any contraindication for IVF/ICSI treatment according to local criteria
* Previous stimulation for IVF/ICSI with \< 4 oocytes obtained
* PCOS
* Undergoing IVF/ICSI for the purpose of fertility preservation
* Allergy towards study drug

Primary outcomes:
measure: Serum progesterone level
timeFrame: Assessed during stimulation treatment on day before hCG injection (throughout the study completion, up to 3 years)
Secondary outcomes:
measure: Serum estradiol, testosterone and androstenedione levels
timeFrame: Assessed on stimulation day 5, day of hCG administration (or the day before), day 7 and 10 after hCG administration. Assessed throughout study completion, up to 3 years.
measure: P and 17-hydroxyprogesterone (17-HP) Area Under the Curve.
timeFrame: Assessed during stimulation treatment throughout the study completion, up to 3 years.
measure: Follicular fluid concentration of estradiol, testosterone, inhibin B and AMH levels
timeFrame: Assessed during stimulation treatment (throughout the study completion, up to 3 years
measure: Total IU of Follicle Stimulating Hormone used per cycle.
timeFrame: Assessed throughout study completion, up to 3 years
measure: Number of follicles > 12 mm
timeFrame: Assessed in stimulated cycle on day of hCG administration or the day before (throughout the study completion), up to 3 years. Cycle length is between 21 and 35 days
measure: Number of oocytes obtained oocytes obtained.
timeFrame: Assessed in stimulated cycle at time of oocyte pick up after follicle aspiration (throughout the study completion, up to 3 years).Cycle length is between 21 and 35 days
measure: Proportion of oocytes resulting in top quality day 2, day 3 embryos or day 5/6 embryos according to validated morphological criteria.
timeFrame: Assessed at day 2-3 after oocyte pick up following stimulation (throughout study completion, up to 3 years)
measure: Oocyte fertilization rate
timeFrame: Assessed during stimulation treatment (throughout the study completion, up to 3 years
measure: Number and quality of embryos obtained, including rate of blastocyst formation.
timeFrame: Assessed during stimulation treatment (throughout the study completion, up to 3 years
measure: Endometrial thickness in millimeters
timeFrame: Assessed throughout the study completion, up to 3 years
measure: Implantation rate
timeFrame: Assessed during stimulation treatment (throughout the study completion, up to 3 years
measure: Biochemical pregnancy rate
timeFrame: Assessed 2 weeks after embryo transfer following stimulation (throughout study completion, up to 3 years)
measure: Clinical pregnancy rate
timeFrame: Pregnancy scan at gestational age week 7-8 (3-4 weeks after the positive hCG in serum). Assessed throughout study completion, up to 3 years.
measure: Morphokinetic parameters of embryo quality as measured using a Time Lapse analysis in centers employing this technology.
timeFrame: Assessed from time of oocyte pick-up to embryo transfer following stimulation (throughout study completion, up to 3 years)
measure: Reported side effects
timeFrame: From start of stimulation and administration of study medication to pregnancy scan week gestational age 7-8. Assessed throughout study completion, up to 3 years.
Other outcomes:
Locations:
city: Herlev
country: Denmark
facility: Unit of Reproductive Medicine, Herlev Hospital
state: Capital Region
city: Copenhagen
country: Denmark
facility: Department of Fertility, Juliane Marie Centeret
state: Capitol Region
city: Hvidovre
country: Denmark
facility: Clinic of Fertility, Hvidovre Hospital
state: Capitol Region
city: Holbæk
country: Denmark
facility: Clinic of Fertility, Holbæk Hospital
state: Region Of Zealand
Study officials:
affiliation: Unit of Reproductive Medicine, Herlev/Gentofte Hospital
name: Sven O. Skouby, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bulow NS, Skouby SO, Warzecha AK, Udengaard H, Andersen CY, Holt MD, Grondahl ML, Nyboe Andersen A, Sopa N, Mikkelsen ALE, Pinborg A, Macklon NS. Impact of letrozole co-treatment during ovarian stimulation with gonadotrophins for IVF: a multicentre, randomized, double-blinded placebo-controlled trial. Hum Reprod. 2022 Jan 28;37(2):309-321. doi: 10.1093/humrep/deab249.