Infertility, Female
Conditions
Brief summary
The goal of this clinical trial is to evaluate a long Clomid protocol as compared to a 5-day Clomid protocol for ovarian stimulation in patients with diminished ovarian reserve undergoing ovarian stimulation for in-vitro fertilization. The aim of the long Clomid protocol is to intensify stimulation of the ovaries and reduce both cost and injection burden for patients. Participants will be randomized to receive the long Clomid protocol vs. the typical protocol involving Clomid only for 5 days followed by growth hormone-releasing hormone (GnRH) antagonist. The primary outcome the investigators will evaluate will be the number of mature eggs retrieved.
Detailed description
Clomiphene citrate (Clomid) is often used for assisted reproductive technologies and may be used to augment ovarian stimulation with exogenous gonadotropins by stimulating pituitary follicle-stimulating hormone (FSH) release in addition. The mechanism of action of Clomid is antagonism at the estrogen receptor, and this stimulates FSH release from the pituitary. The typical Clomid-based protocol has involved clomid only given for the first five days of stimulation to allow for endometrial development later in the cycle for a fresh embryo transfer following the oocyte retrieval. This protocol involves the addition of a GnRH antagonist medication later in the cycle to prevent premature ovulation. Recent national trends in IVF, however, have moved towards frozen embryo transfers and use of preimplantation genetic testing, which obviates any concerns regarding the endometrium. Recent experience in our clinic has suggested that Clomid may also prevent premature ovulation by antagonizing the positive feedback that is responsible for the luteinizing hormone (LH) surge and ovulation. Given in this manner, Clomid can be given throughout the duration of an ovarian stimulation cycle, achieve higher FSH levels and degree of ovarian stimulation in patients with diminished ovarian reserve, and obviate the need for GnRH antagonist medication (another expensive subcutaneous injection). The objective of this study is to compare a "long Clomid protocol" (i.e. using Clomid throughout the entire duration of the IVF cycle) as compared to the typical 5-day clomid protocol. The investigators hypothesize that the long Clomid protocol will be non-inferior to the typical five-day course and obviate the need for GnRH antagonist by preventing premature ovulation. Patients with diminished ovarian reserve and anticipated poor response to ovarian stimulation will be randomized to the long Clomid protocol vs. a 5-day Clomid with GnRH antagonist protocol. The primary outcome will be oocyte yield. Secondary outcome will be premature ovulation, embryo development, and pregnancy outcomes. Please note that participants are responsible for treatment costs if they take part in this study. Our clinic Financial Team will be happy to discuss treatment costs and determine your insurance coverage at your initial consultation.
Interventions
DRUGClomiphene Citrate
Clomiphene citrate is an estrogen receptor antagonist that leads to pituitary FSH release and prevention of the LH surge.
Sponsors
University of Southern California
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients will be randomized to the two treatment arms
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 44 Years
Healthy volunteers
No
Inclusion criteria
* Undergoing IVF * Must meet POSEIDON criteria based on clinic evaluation * Female partner: Antral follicle count of 2 or more and age \<45 at time of stimulation start * Male partner/sperm source: Cannot be azoospermic * Planning freeze-all cycle (regardless of blastocyst or cleavage stage culture) or fresh transfer if randomized to short Clomid group * Planning 36-hour trigger window
Exclusion criteria
* Normal ovarian reserve or good response * Allergy or adverse reaction to Clomid * Minimal stimulation protocols * History of prior premature ovulation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of mature oocytes | Up to 1 month after study completion | The number of mature oocytes retrieved at oocyte retrieval |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants that experience premature ovulation | Up to 1 month after study completion | Premature LH surge, progesterone rise and estradiol decrease, or evidence of premature ovulation (no oocytes on retrieval or free fluid and follicular collapse on ultrasound) |
| Number of oocytes that get fertilized and grow to the blastocyst stage | Up to 1 month after study completion | Fertilization rate and blastulation |
| Pregnancy outcomes | Up to 3 years after study completion | Clinical pregnancy rate, ongoing pregnancy rate, live birth rate |
Countries
United States
Contacts
CONTACTBonnie Song, MD
CONTACTRachel Mandelbaum
PRINCIPAL_INVESTIGATORRichard Paulson
paulsonivf@havingbabies.com
Outcome results
None listed