Effect of Addition of Aromatase Inhibitor to Ovarian Stimulation Therapy in IVF Treatment

Conditions

Infertility

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

Nathalie Søderhamn Bülow, Agnieszka Katarzyna Warzecha, Mette Villads Nielsen, Claus Yding Andersen, Marianne Dreyer Holt et al. (13 authors)

Human Reproduction2023-09-1212 citations

10.1093/humrep/dead182

O-126 Impact of letrozole cO-treatment during ovarian stimulation on the oocyte yield, embryo development, and live birth rate – a randomised controlled trial (RIOT)

Niels Bülow, Agnieszka Katarzyna Warzecha, Mette Villads Nielsen, Claus Yding Andersen, Marianne Dreyer Holt et al. (13 authors)

Human Reproduction2022-06-29

10.1093/humrep/deac105.026

Impact of letrozole co-treatment during ovarian stimulation with gonadotrophins for IVF: a multicentre, randomized, double-blinded placebo-controlled trial

Nathalie Søderhamn Bülow, Sven O. Skouby, Agnieszka Katarzyna Warzecha, Hanne Udengaard, Claus Yding Andersen et al. (12 authors)

Human Reproduction2021-10-2739 citations

10.1093/humrep/deab249

O-229 Impact of letrozole co-treatment during ovarian stimulation with gonadotropins for in vitro fertilisation (IVF): a multicentre, randomised, double-blinded placebo-controlled trial

Nathalie Søderhamn Bülow, Sven O. Skouby, Agnieszka Katarzyna Warzecha, Hanne Udengaard, Claus Yding Andersen et al. (12 authors)

Human Reproduction2021-07-011 citations

10.1093/humrep/deab128.053

Interventions

DRUGLetrozole

Adjuvant therapy to recFSH during ovarian stimulation

DRUGPlacebo

Adjuvant therapy to recFSH during ovarian stimulation

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

FEMALE

Age

18 Years to 40 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame
Serum progesterone level	Assessed during stimulation treatment on day before hCG injection (throughout the study completion, up to 3 years)

Secondary

Measure	Time frame
P and 17-hydroxyprogesterone (17-HP) Area Under the Curve.	Assessed during stimulation treatment throughout the study completion, up to 3 years.
Follicular fluid concentration of estradiol, testosterone, inhibin B and AMH levels	Assessed during stimulation treatment (throughout the study completion, up to 3 years
Total IU of Follicle Stimulating Hormone used per cycle.	Assessed throughout study completion, up to 3 years
Number of follicles > 12 mm	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
Number of oocytes obtained oocytes obtained.	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
Proportion of oocytes resulting in top quality day 2, day 3 embryos or day 5/6 embryos according to validated morphological criteria.	Assessed at day 2-3 after oocyte pick up following stimulation (throughout study completion, up to 3 years)
Oocyte fertilization rate	Assessed during stimulation treatment (throughout the study completion, up to 3 years
Serum estradiol, testosterone and androstenedione levels	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.
Endometrial thickness in millimeters	Assessed throughout the study completion, up to 3 years
Implantation rate	Assessed during stimulation treatment (throughout the study completion, up to 3 years
Biochemical pregnancy rate	Assessed 2 weeks after embryo transfer following stimulation (throughout study completion, up to 3 years)
Clinical pregnancy rate	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.
Morphokinetic parameters of embryo quality as measured using a Time Lapse analysis in centers employing this technology.	Assessed from time of oocyte pick-up to embryo transfer following stimulation (throughout study completion, up to 3 years)
Reported side effects	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.
Number and quality of embryos obtained, including rate of blastocyst formation.	Assessed during stimulation treatment (throughout the study completion, up to 3 years

Countries

Denmark

Outcome results

None listed