Clinical Trials Logo

Clinical Trial 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.


Clinical Trial Description

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. Patients will be randomized to one of two possible stimulation cycles as will be described. Luteal Phase Ovarian Stimulation (LPOS) Patients will present for an appointment on approximately day 15-18 of her menstrual cycle. If serum progesterone >3 ng/mL, and bHCG < 5 mIU/mL, the patient will begin 450 IU of daily injectable gonadotropins: 150 IU of hMG (Menopur®, Ferring Pharmaceuticals) and 300 IU of recombinant FSH (rFSH) (Gonal F®,Serono; or Follitropin beta (Follistim®, Organo)). The specific rFSH chosen will be based on the individual patient's insurance coverage. The patient will perform daily injections during the course of her stimulation, and will also take oral Clomiphene citrate 100mg daily for the first five days of the stimulation. FSH dose will be titrated during the stimulation (per physician discretion) based on serum estradiol levels and ovarian response to a minimum of no gonadotropins and a maximum of 600 IU daily. She will present for follicular monitoring ultrasound and serum blood tests on stimulation day 3-4, 5-6, and 7-8-~15. Gonadotropin releasing hormone (GnRH) antagonist (Ganirelix, Organon; and cetrorelix, Serono) will be started daily once either (1) serum estradiol level reaches > 400 pg/mL, lead follicle size > 13mm, or (2) on stimulation day 6. Once patient are ready for ovulation trigger as determine by physician, 5-10,000 units of human chorionic gonadotropin (Novarel®: Ferring Pharmaceuticals; or Pregnyl®: Schering-Plough) will be administered. A patient's trigger shot could be changed to include a GnRH agonist (i.e Luprolide acetate 40 IU) if deemed clinically necessary for ovarian hyperstimulation syndrome prevention. On the morning after hCG administration, patients' blood will be drawn and serum analyzed for hCG concentration to ensure adequate absorption (mean time 8-10 hours). Transvaginal oocyte retrieval will be performed 35 to 37 hours after hCG trigger. All metaphase II oocytes will be fertilized with intracytoplasmic sperm injection (ICSI) or IVF per patient request and laboratory protocol. Embryos will be cultured to the blastocyst stage and vitrified on day 5-7. If patient requests preimplantation genetic testing for aneuploidy (PGT-A), an embryo biopsy will be performed on day 5-7 of development prior to vitrification, and biopsy specimen will be sent to an outside laboratory for chromosome analysis. Luteal Estradiol priming protocol (E2 prime) Patients will present for an appointment on approximately day 18-21 of her menstrual cycle. If serum progesterone >3 ng/mL, and bHCG < 5 mIU/mL, the patient will begin Estradiol patches (Vivelle Dot 0.1mg, Novartis Pharmaceuticals; or Climara, Bayer) and change them every other day. She will also take daily Gonadotropin releasing hormone (GnRH) antagonist (Ganirelix, Organon; and cetrorelix, Serono) for the following three days. Patients will then present for a baseline appointment with onset of her menses. If serum progesterone < 1.0 ng/mL, and bHCG < 5 mIU/mL, on cycle day 2-3 the patient will stop her estrogen patches and start 450 IU of daily injectable gonadotropins: 150 IU of hMG (Menopur®, Ferring Pharmaceuticals) and 300 IU of recombinant FSH (rFSH) (Gonal F®,Serono; or Follitropin beta (Follistim®, Organo)). The specific rFSH chosen will be based on the individual patient's insurance coverage. Estrogen patch will be removed the day of starting gonadotropin injections. The patient will perform daily injections during the course of her stimulation, and will also take oral Clomiphene citrate 100mg daily for the first five days of the stimulation. FSH dose will be titrated during the stimulation (per physician discretion) based on serum estradiol levels and ovarian response to a minimum of no gonadotropins and a maximum of 600 IU daily. She will present for follicular monitoring ultrasound and serum blood tests on stimulation day 3-4, 5-6, and 7-8-~15. Gonadotropin releasing hormone (GnRH) antagonist (Ganirelix, Organon; and cetrorelix, Serono) will be started daily once either (1) serum estradiol level reaches > 400 pg/mL, lead follicle size > 13mm, or (2) on stimulation day 6. Once patient are ready for ovulation trigger as determine by physician, 5-10,000 units of human chorionic gonadotropin (Novarel®: Ferring Pharmaceuticals; or Pregnyl®: Schering-Plough) will be administered. A patient's trigger shot could be changed to include a GnRH agonist (i.e Luprolide acetate 40 IU) if deemed clinically necessary for ovarian hyperstimulation syndrome prevention. On the morning after hCG administration, patients' blood will be drawn and serum analyzed for hCG concentration to ensure adequate absorption (mean time 8-10 hours). Transvaginal oocyte retrieval will be performed 35 to 37 hours after hCG trigger. All metaphase II oocytes will be fertilized with intracytoplasmic sperm injection (ICSI) or IVF per patient request and laboratory protocol. Embryos will be cultured to the blastocyst stage and vitrified on day 5-7. If patient requests preimplantation genetic testing for aneuploidy (PGT-A), an embryo biopsy will be performed on day 5-7 of development prior to vitrification, and biopsy specimen will be sent to an outside laboratory for chromosomal analysis. Outcomes between the two stimulation protocols will be compared. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT04447872
Study type Interventional
Source Northwell Health
Contact Baruch Abittan, MD
Phone 5165621735
Email babittan2@northwell.edu
Status Recruiting
Phase N/A
Start date September 15, 2020
Completion date June 2025

See also
  Status Clinical Trial Phase
Completed NCT03607409 - Role of Inhibin A as Biomarker for Ovarian Response for IVF Treatment
Recruiting NCT02312076 - GnRHa for Luteal Phase Support in Long GnRHa Protocol Cycles Phase 4
Terminated NCT02161861 - Improvement of IVF Fertilization Rates, by the Cyclic Tripeptide FEE - Prospective Randomized Study N/A
Completed NCT03287479 - Comparison of a Semi-automated Closed Vitrification System (Gavi®) With a Manual Open Vitrification Sytem (Cryotop®) N/A
Terminated NCT03522350 - Randomized Trial Comparing EmbryoScope With EmbryoScope+. N/A
Completed NCT04496284 - Embryo Transfer Outcomes After Vitrification With Slush Nitrogen Compared to Liquid Nitrogen N/A
Completed NCT03623659 - pArtiaL zonA pelluciDa Removal by assisteD hatchINg of Blastocysts N/A
Completed NCT03895099 - New Ovarian Stimulation With Random Start, Use of Progestin Protocol for Oocyte Donors Phase 3
Active, not recruiting NCT04142112 - Randomized, Standard-Controlled, Study to Evaluate the Ohana IVF Sperm Preparation Kit, SPeRtility IVF Next Generation N/A
Completed NCT03152643 - Cumulative Live Birth Rates After Cleavage-stage Versus Blastocyst-stage Embryo Transfer N/A
Recruiting NCT03683771 - Assessment of Endometrial Pattern and Sub-endometrial Vascularity in ICSI Outcome
Recruiting NCT03161119 - Comparing Two Different Embryo Transfer Catheters N/A
Completed NCT04108039 - Micronized Progesterone vs Gonadotropin-releasing Hormone (GnRH) Antagonist in Freeze-all IVF Cycles. N/A
Completed NCT03677492 - Supplementing Intracytoplasmic Sperm Injection Handling Medium With Cytochalasin D ( ICSI-CD) N/A
Completed NCT03678584 - Supplementing Intracytoplasmic Sperm Injection Handling Medium With Chaetoglobosin A ( ICSI-CA) N/A
Completed NCT03678597 - Supplementing Intracytoplasmic Sperm Injection Handling Medium With Latrunculin B ( ICSI-LB) N/A
Completed NCT03678610 - Handling Medium for ICSI With Ionomycin and Latrunculin A N/A
Completed NCT03678571 - Oocyte Vitrification Aided With Latrunculin A N/A
Completed NCT03678558 - Oocyte Vitrification Aided With Cytochalasin B N/A
Completed NCT03678818 - Supplementing Intracytoplasmic Sperm Injection Handling Medium With Latrunculin A (ICSI-LA) N/A