Use of Clomiphene Citrate as an Inhibitor of Ovulation in an Oocyte Cryopreservation Cycle (CCOI)

In vitro fertilization (IVF) has helped countless couples conceive where they otherwise were unable, but does come at a significant cost. A large portion of that cost is in the medications that allow for controlled ovarian hyperstimulation. One aspect of treatment is in ovulation inhibition to allow for supraphysiologic recruitment of oocytes prior to natural ovulation. Historically, GnRH agonist and antagonists have been used. However, these are subcutaneous injections and can be costly. Clomiphene citrate is a selective estrogen receptor modulator that acts as an estrogen antagonist in the hypothalamus and pituitary and is an inexpensive oral agent. It may be used as an inhibitor of ovulation in IVF in theory but this has never been attempted to the best of our knowledge.

Study Overview

• Status: Not yet recruiting
• Conditions: Infertility; Infertility, Female
• Intervention / Treatment: Drug: Clomiphene

Detailed Description

In vitro fertilization (IVF) has been used for over 40 years in treating infertility, and with the advent of cryopreservation, it is now possible to stimulate, retrieve and freeze oocytes for use at a later date. In fact, in late 2012 the FDA removed the experimental label from oocyte cryopreservation (OC), allowing for OC cycles to become a standard of care for patients with conditions that threaten their ovarian reserve or patients who wish to preserve their fertility electively. Currently, standard stimulation protocols for superovulation of oocytes for OC involve subcutaneous injections of GnRH agonists or antagonists to inhibit premature natural ovulation as the higher number of oocytes are recruited with gonadotropins. These medications are costly and cumbersome and therefore it is of interest to design protocols that are both easier on patient compliance and more cost effective.

Clomiphene citrate is a selective estrogen receptor modulator (SERM). It selectively binds to estrogen receptors in the hypothalamus, pituitary, ovary, endometrium, and cervix producing estrogenic and anti-estrogenic effects. However the exact mechanism of clomid is poorly understood. Multiple studies have been done through animal models. One studied showed that it inhibits the negative feedback of endogenous estrogen to subsequently increase secretion of GnRH. It is also shown to increase the frequency of GnRH, however not the amplitude [Wallach]. Current IVF protocols use either GnRH antagonist or agonist to inhibit premature ovulation. Therefore due to Clomid effect on both the hypothalamus and pituitary it could theoretically block ovulation if taken continuously to down regulate the GnRH receptors.

A study published in 1982 by Marut and Hodgen looked at the effect of high doses clomiphene in primates with normal cycles. Using high dose clomiphene (25mg daily) for five days then evaluated gonadotropins, estrogen, progesterone and preformed serial laparoscopies. In all 18 of the treatment cycles there was a delay in ovulation. Upon literature review, no other studies had been conducted looking using clomiphene citrate as a medication to inhibit ovulation during an ovarian stimulation cycle.

• Study Type: Observational
• Enrollment (Anticipated): 10

Contacts and Locations

Study Locations

• United States
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70817
      • Womans Hospital
      • Contact: Neil R Chappell, MD, MSCI; Phone Number: 225-926-6886; Email: nchappell@fertilityanswers.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Patients who are interested in elective oocyte cryopreservation as a pilot group to investigate the feasibility of using clomiphene as an ovulation inhibitor.

Description

Inclusion Criteria:

• Female
• 18-42 years old, inclusive
• Planning to undergo IVF with egg retrieval for oocyte cryopreservation

Exclusion Criteria:

• Tobacco or illicit drug use
• History of infertility
• Prior failed IVF or OC cycle
• Drug allergy to Clomid
• Hypertension
• Migraine with aura

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ovulation	Evidence of premature ovulation during IVF stimulation	3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oocyte yield	Number of oocytes from IVF cycle	3 weeks
Maturity Rate	% of eggs mature / # of oocytes collected	3 weeks
Side effects	Number of patients reporting side effects of medication	3 weeks

Collaborators and Investigators

• Sponsor: Neil Chappell

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2023
• Primary Completion (Anticipated): June 30, 2024
• Study Completion (Anticipated): October 31, 2024

Study Registration Dates

• First Submitted: May 9, 2023
• First Submitted That Met QC Criteria: May 17, 2023
• First Posted (Actual): May 19, 2023

Study Record Updates

• Last Update Posted (Actual): May 19, 2023
• Last Update Submitted That Met QC Criteria: May 17, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility; Infertility, Female; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Estrogen Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Clomiphene
• Other Study ID Numbers: Womans

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No