Recruiting

Luteal Stimulation vs. Estrogen Priming

Sponsor:

Northwell Health

Code:

NCT04447872

Conditions

Infertility

Diminished Ovarian Reserve

IVF

Eligibility Criteria

Sex: Female

Age: 20 - 45

Healthy Volunteers: Not accepted

Interventions

Timing of injectable gonadotropins

Study Details

Brief summary:

Ovarian reserve defines the quantity and quality of the ovarian primordial follicular pool. Diminished ovarian reserve (DOR) indicates a reduction in the quantity of ovarian follicular pool to less than expected for age. It is an important cause of infertility in many couples.

To date, there is no clear consensus in the literature on the definition of diminished ovarian reserve, and it is unclear whether low oocyte yield results from an abnormal atresia rate of the follicle pool, or from a lower follicle pool at birth or whether it can just occur as a normal variation in the population.

The ovarian response to controlled ovarian stimulation with gonadotropins (for example, for in vitro fertilization) is largely determined by the ovarian reserve, and there are numerous different ovarian stimulation protocols that are employed to try and increase the oocyte yield of a particular cycle. There is no consensus on which, if any, of these protocols are superior and preferred for patient with DOR.

Luteal gonadotropin stimulation is a protocol of controlled ovarian stimulation (COS) for use in assisted reproductive technologies (ART) that has emerged over the past decade as an acceptable alternative to the classic follicular gonadotropin stimulation.

The luteal estradiol patch protocol was introduced in 2005 in patients with poor response to controlled ovarian stimulation (COS) and to address the phenomenon of early follicle recruitment in patients with diminished ovarian reserve (DOR). Luteal gonadotropin stimulation can potentially achieve the same effect by initiating follicular recruitment for IVF prior to the body's own premature recruitment.

Our hypothesis is that the luteal stimulation protocol and estradiol priming protocol are equivalent with regard to the outcome of number of mature oocytes retrieved. Patients who will be undergoing controlled ovarian stimulation and who have a diagnosis of diminished ovarian reserve will be considered for this trial, and enrolled if meeting all inclusion and no exclusion criteria.

Conditions

Infertility

Diminished Ovarian Reserve

IVF

Study ID

NCT04447872

Start date

Sep 15, 2020

Status verified date

Oct, 2023

Completion date

Jun, 2025

Anticipated

Primary completion date

Jun, 2025

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Female

Age: 20 - 45

Healthy Volunteers: Not accepted

Inclusion Criteria:

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Female aged 20 - 45
4. Regular menstrual cycles between 21 and 40 days
5. Presence of both ovaries
6. Meets criteria for DOR by the recent ASRM/ACOG Committee Opinion

1. antimüllerian hormone (AMH) value less than 1 ng/mL
2. antral follicle count less than 5-7 and
3. follicle-stimulating hormone (FSH) greater than 10 IU/L or
4. a history of poor response to in vitro fertilization stimulation (fewer than four oocytes at time of egg retrieval).

Exclusion Criteria:

1. Oocyte donation cycle
2. Oocyte freezing cycle
3. Current ovarian cyst > 3cm
4. Anovulatory or oligo-ovulatory (<6 ovulation per year)
5. Previous oophorectomy
6. Exposure to cytotoxic or pelvic irradiation
7. Planned aromatase inhibitor usage during current ovarian stimulation
8. Sensitizing or ovarian stimulating therapy in the past one month

Additional contraindications to this study re, as follows (because such patients cannot receive an estrogen patch):
9. Undiagnosed abnormal genital bleeding
10. Known, suspected, or history of breast cancer
11. Known or suspected estrogen-dependent neoplasia
12. Active DVT, PE, or a history of these conditions
13. Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions
14. Known anaphylactic reaction or angioedema with estradiol patches
15. Known liver impairment or disease
16. Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders

Study Design

Enrollment

142 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Luteal phase ovarian stimulation (LPOS)

Patients will present in the luteal phase, and will begin 150 IU hMG and 300 IU recombinant FSH daily, as well as oral Clomiphene citrate 100mg daily for the first five days of the stimulation. FSH can then be titrated per patient response. Gonadotropin releasing hormone antagonist (Ganirelix, Organon; and cetrorelix, Serono) will be started per criteria. Once patients are ready for ovulation trigger, 5-10,000 units of human chorionic gonadotropin, +/- GnRH agonist (i.e Luprolide acetate 40 IU), will be administered. All metaphase II oocytes obtained by oocyte retrieval will be fertilized with intracytoplasmic sperm injection (ICSI) or IVF. Embryos will be cultured to the blastocyst stage and vitrified on day 5-7 with or without embryo biopsy for genetic analysis.

active comparator: Luteal estradiol priming protocol

In the luteal phase, the patient will begin Estradiol patches 0.1mg QOD. She will also take daily Gonadotropin releasing hormone (GnRH) antagonist (Ganirelix, Organon; and cetrorelix, Serono) for three days. With menses, she will begin 150 IU hMG, 300 IU recombinant FSH daily, and oral Clomiphene citrate 100mg qd (for five days). FSH can be titrated per patient response. GnRH antagonist will be started per criteria. 5-10,000 units of human chorionic gonadotropin, +/- GnRH agonist (i.e Luprolide acetate 40 IU) will be administered for ovulation trigger. All metaphase II oocytes obtained by oocyte retrieval will be fertilized with intracytoplasmic sperm injection (ICSI) or IVF. Embryos will be cultured to the blastocyst stage and vitrified on day 5-7 with or without embryo biopsy for genetic analysis.

Interventions

Timing of injectable gonadotropins

Gonadotropins will with be started in the luteal phase or in follicular phase (preceded by Estradiol patches)

Primary outcome measure

  • Number of mature (Metaphase II) oocytes retrieved [ Time Frame: First day after oocyte retrieval ]

Central Contacts and Locations

Central contacts

Baruch Abittan, MD

5165621735babittan2@northwell.edu

Locations

Northwell Fertility

Recruiting

Manhasset, New York, United States, 11030

Contacts

Baruch Abittan, MD

516-562-1735babittan2@northwell.edu

More Information

Sponsor

Northwell Health

Last update posted

Oct 16, 2023

Last verified

Oct, 2023

Keywords

  • IVF
  • In Vitro Fertilization
  • DOR
  • Diminished Ovarian Reserve
  • Controlled ovarian stimulation

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-03. This information was provided to ClinicalTrials.gov by Northwell Health on 2023-10-16.