Effect of Different Ovarian Stimulation Protocols on Endometrial Receptivity

NCT03755973 | Completed Phase 4

• 1 other identifier: 1806-LIS-044-SD
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This study will assess the change in endometrial gene expression signature on the day of embryo transfer according to the type of exogenous gonadotropins administered.

Conditions

Infertility, Female; Endometrial Diseases

Keywords

Endometrial receptivity; Ovarian stimulation

Outcome Measures

Primary Outcomes (1)

• Endometrial gene expression signature on the day of embryo transfer

  RNA sequencing of specimen of endometrium

  7 days after the last day of ovarian stimulation

Secondary Outcomes (1)

• Serum concentrations of progesterone from the start of stimulation until the day of embryo transfer

  3 weeks

Study Arms (3)

CFA plus step-down rFSH (1A)

EXPERIMENTAL

A single dose of 150 IU of CFA followed by daily rFSH will be administered. The initial rFSH administration will be dosed between 100 IU and 200 IU according to the following criteria: * 200 or 300 IU: \<3 follicles above 13 mm visible on transvaginal ultrasound; * 150 IU, \>2 follicles above 13 mm and circulating day-8 follicle-stimulating hormone (FSH) levels ≤20 IU/mL. * 100 IU, \>2 follicles above 13 mm and circulating day-8 FSH levels \>20 IU/mL; Subjects will perform a step-down daily rFSH dose (fixed decreases in the dosing of 25 IU/day) until the triggering criteria are met or a minimum of 50 IU/day is reached. Subjects with \<3 follicles above 13 mm visible will maintain 200 IU/day of rFSH until this criterion is met, initiating a fixed 25 IU/day stepdown protocol only from then onwards.

Drug: CFA; Drug: rFSH; Procedure: Step-down daily rFSH dose

CFA plus fixed daily dose rFSH (1B)

EXPERIMENTAL

A single dose of 150 IU of CFA followed by a fixed daily rFSH dosing protocol of 200 or 300 IU will be administered as ovarian stimulation

Drug: CFA; Drug: rFSH; Procedure: Fixed daily rFSH dosing protocol of 200-300 IU

Fixed daily dose rFSH only

ACTIVE COMPARATOR

A fixed daily rFSH dosing protocol of 200 or 300 IU will be administered as ovarian stimulation

Drug: rFSH; Procedure: Fixed daily rFSH dosing protocol of 200-300 IU

Interventions

CFA DRUG

Long-acting exogenous ovarian stimulation

Also known as: Corifollitropin alpha

CFA plus fixed daily dose rFSH (1B); CFA plus step-down rFSH (1A)

rFSH DRUG

Daily rFSH

Also known as: Puregon, Follitropin beta

CFA plus fixed daily dose rFSH (1B); CFA plus step-down rFSH (1A); Fixed daily dose rFSH only

Fixed daily rFSH dosing protocol of 200-300 IU PROCEDURE

The dose of daily rFSH is fixed at 200 or 300 IU

CFA plus fixed daily dose rFSH (1B); Fixed daily dose rFSH only

Step-down daily rFSH dose PROCEDURE

The dose of daily rFSH is progressively reduced

CFA plus step-down rFSH (1A)

Eligibility Criteria

• Age: 18 Years - 42 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Informed consent form (ICF) dated and signed.
• Age: ≥18 and ≤42 years old.
• AFC \<20.
• Body Mass Index (BMI): ≥18.5 Kg/m2 and \<30 Kg/m2.
• Weight: ≥50 kg and \<80 kg.
• First or second ART cycle (with pregnancy wish and planned for single blastocyst transfer) at the study site, or fertility preservation cycle.
• Regular menstrual cycles (between 22 and 35 days).
• Two ovaries present.

You may not qualify if:

• Simultaneous participation in another clinical study.
• Previous history of poor ovarian response (\<4 oocytes retrieved) with a maximal dose of OS (≥300 IU/day) or OHSS, regardless of gonadotropin dose.
• Known reasons for impaired implantation (i.e. hydrosalpinx, fibroid distorting the endometrial cavity, Asherman's syndrome, thrombophilia or endometrial tuberculosis).
• Repeated miscarriages (\>2 previous biochemical pregnancies or \>2 spontaneous miscarriages).
• Recurrent implantation failure (\>3 failed cycles with good quality embryos).
• Polycystic ovary syndrome (PCOS).
• Tumours of the ovary, breast, uterus, pituitary or hypothalamus.
• Abnormal (not menstrual) vaginal bleeding without a known/diagnosed cause.
• Ovarian cysts or enlarged ovaries.
• Fibroid tumours of the uterus incompatible with pregnancy.
• Malformations of the reproductive organs incompatible with pregnancy.
• Primary gonadal failure.
• Renal impairment defined as estimated glomerular filtration rate of 90 ml/min/1.73 m2 determined by the Modified Diet and Renal Disease (MDRD) equation at screening.
• Previous antibiotic hypersensitivity reactions (streptomycin and/or neomycin).
• Risk factors for thromboembolic events, such as a personal or family history, severe obesity or thrombophilia.

Sponsors & Collaborators

• Instituto Valenciano de Infertilidade de Lisboa: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Instituto Valenciano de Infertilidade

Lisbon, Portugal

Location

MeSH Terms

Conditions

Infertility, Female; Uterine Diseases

Interventions

follitropin beta

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Infertility

Study Officials

• Samuel Santos-Ribeiro, MD PhD

  Instutito Valenciano de Infertilidade de Lisboa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: All consenting subjects will first undergo an endometrial biopsy seven days after the luteinizing hormone (LH) peak in an unmedicated natural cycle. This biopsy will serve as the baseline endometrial biopsy (natural cycle biopsy) for the gene expression signature analysis. Following this baseline biopsy, the subjects will be randomly allocated to a specific type of ovarian stimulation regimen in order to later perform some second endometrial biopsy, five days after oocyte retrieval (stimulated cycle biopsy).

Study Record Dates

• First Submitted: November 26, 2018
• First Posted: November 28, 2018
• Study Start: January 29, 2020
• Primary Completion: May 22, 2023
• Study Completion: May 22, 2023
• Last Updated: June 1, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

PT (1)