Clinical trial NCT06701071: Evaluation of a Long Versus Short Clomid Protocol for Controlled Ovarian Stimulation
Official title: Evaluation of a Long Versus Short Clomid Protocol for Controlled Ovarian Stimulation in Patients with Diminished Ovarian Reserve Undergoing In-vitro Fertilization: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Infertility, Female
Lead sponsor: University of Southern California
Sponsor class: OTHER
First posted: 2024-11-22
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 46
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomized to the two treatment arms
Primary purpose: TREATMENT

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 or egg freezing. 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 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.

Eligibility criteria: Inclusion Criteria:

* Diminished ovarian reserve
* Prior poor response to ovarian stimulation

Exclusion Criteria:

* Normal ovarian reserve or good response
* Allergy or adverse reaction to clomid
* Minimal stimulation protocols
* History of prior premature ovulation

Primary outcomes:
measure: Number of mature oocytes
timeFrame: Up to 1 month after study completion
Secondary outcomes:
measure: Number of participants that experience premature ovulation
timeFrame: Up to 1 month after study completion
measure: Number of oocytes that get fertilized and grow to the blastocyst stage
timeFrame: Up to 1 month after study completion
measure: Pregnancy outcomes
timeFrame: Up to 3 years after study completion
Other outcomes:
Locations:
city: Pasadena
country: United States
facility: HRC Fertility
state: California
Study officials:
affiliation: rpaulson@med.usc.edu
name: Richard Paulson
role: PRINCIPAL_INVESTIGATOR
References: