Dopamine D-2 Antagonist Use in Poor Responders in IVF: a Randomized Controlled Trial

NCT02262923 | Withdrawn

• 1 other identifier: 14-0209-A
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Metoclopramide is a dopamine D2 receptor antagonist with antiemetic and gastrokinetic properties which has been approved for use in pregnant women. Women with polycystic ovary syndrome (PCOS) have been found to have lower dopaminergic tone and increased ovarian vascularity and vascular endothelial growth factor (VEGF) levels compared to controls. During ovarian stimulation, PCOS patients exhibit greater sensitivity to gonadotropins and increased follicular development. Administration of dopamine D2 antagonists may mimic the low dopaminergic tone noted in PCOS patients, increase VEGF levels, angiogenesis, and subsequently improve follicular growth during ovarian stimulation. This strategy could be used to improve IVF outcomes in poor responders. The investigators hypothesize that, compared to gonadotropin use alone, the use of metoclopramide in combination with gonadotropins in poor responders undergoing IVF will result in an increased number of mature oocytes obtained at oocyte retrieval and improved IVF outcomes.

Conditions

in Vitro Fertilization; Poor Responder

Outcome Measures

Primary Outcomes (1)

• Number of oocytes retrieved

  1 year

Secondary Outcomes (9)

• Number of mature follicles (≥1.5cm) seen on transvaginal ultrasound at the time of ovulation trigger

  1 year

• Peak serum estradiol levels measured at the time of ovulation trigger shot

  1 year

• Ratio of mature/ immature oocytes obtained at oocyte retrieval

  1 year

• Follicular fluid levels of VEGF, VEGFR-1 and VEGFR-2

  1 year

• Total dose of gonadotropins used and number of days of stimulation

  1 year

Study Arms (2)

Control

NO INTERVENTION

Poor responders will be defined as women who have undergone a previous IVF cycle with fewer than 4 oocytes retrieved and at least one of the following two criteria: (1) advanced age (≥40 years) or any other risk factor for poor ovarian response and (2) abnormal ovarian reserve testing (antral follicle count (AFC) \< 5-7 or anti-mullerian hormone (AMH) level \< 3.6-7.9 pmol/L). Poor responders who will be undergoing a repeat IVF cycle will be recruited for the study with informed consent. In the control arm, patients will undergo the same ovarian stimulation protocol as the previous IVF cycle in which they experienced a poor response. Starting 3 weeks prior to the first day of stimulation until the time of ovulation trigger (approximately 5 weeks overall), these patients will receive an oral placebo three times daily.

Experimental

EXPERIMENTAL

Poor responders will be defined as women who have undergone a previous IVF cycle with fewer than 4 oocytes retrieved and at least one of the following two criteria: (1) advanced age (≥40 years) or any other risk factor for poor ovarian response and (2) abnormal ovarian reserve testing (antral follicle count (AFC) \< 5-7 or anti-mullerian hormone (AMH) level \< 3.6-7.9 pmol/L). Poor responders who will be undergoing a repeat IVF cycle will be recruited for the study with informed consent. In the experimental arm, patients will undergo the same ovarian stimulation protocol as the previous IVF cycle in which they experienced a poor response. Starting 3 weeks prior to the first day of stimulation until the time of ovulation trigger (approximately 5 weeks in total), these patients will receive oral metoclopramide 5mg three times daily..

Drug: metoclopramide

Interventions

metoclopramide DRUG

Experimental

Eligibility Criteria

• Age: 21 Years - 43 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Poor responders undergoing a repeat IVF cycle defined as women who have undergone at least one previous IVF cycle with fewer than 4 oocytes retrieved and at least one of the following:
• Advanced age (≥40 years) or any other risk factor for poor ovarian response
• Abnormal ovarian reserve testing (antral follicle count (AFC) \< 5-7 or anti-mullerian hormone (AMH) level \< 3.6-7.9 pmol/L)

You may not qualify if:

• Subjects who have previously been recruited into this study and either had cycle cancellation, underwent retrieval or dropped out of the study.
• Women with contraindications or allergies to metoclopramide.
• Women with elevated prolactin levels or known to have pituitary microadenomas or macroadenoma.
• Women who are taking dopamine agonist medications.

Sponsors & Collaborators

• Mount Sinai Hospital, Canada: lead

Study Sites (1)

Mount Sinai Hospital

Toronto, Ontario, M5T 3H7, Canada

Location

MeSH Terms

Interventions

Metoclopramide

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; para-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Chlorobenzoates; Hydroxybenzoate Ethers; Hydroxybenzoates; Hydroxy Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenyl Ethers; Phenols

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2014
• First Posted: October 13, 2014
• Study Start: March 1, 2016
• Primary Completion: March 1, 2018
• Study Completion: March 1, 2018
• Last Updated: April 11, 2022

Record last verified: 2019-03

Locations

CA (1)