Evaluation of a Long Versus Short Clomid Protocol for Controlled Ovarian Stimulation

Phase 4

Not yet recruiting

• Conditions: Infertility, Female
• Interventions: Drug: Clomiphene Citrate

• Registration Number: NCT06701071
• Lead Sponsor: University of Southern California

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.

Study Timeline

• Study First Submitted: 2024-06-13
• Status Verified: 2024-11
• Study First Submitted QC: 2024-11-19
• Last Update Submitted: 2024-11-19
• Study First Posted: 2024-11-22
• Last Update Posted: 2024-11-22
• Study Start: 2024-12
• Primary Completion: 2025-09
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 60

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Long Clomid	Clomiphene Citrate	Clomid with gonadotropins throughout the entire duration of ovarian stimulation without addition of GnRH antagonist
5-day Clomid	Clomiphene Citrate	Clomid only for 5 days starting on day 2 or 3 of menses with gonadotropins, with GnRH antagonist added when the lead follicle reaches \~14mm.

Primary Outcome Measures

Name	Time	Method
Number of mature oocytes	Up to 1 month after study completion	The number of mature oocytes retrieved at oocyte retrieval

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

HRC Fertility; 🇺🇸 Pasadena, California, United States