Efficacy Study Comparing the Effect of Clomiphencitrate to an Antagonist Protocol (CANTAPOR)

Prospective Randomized Phase IV Study Comparing the Effect of Adding Clomiphencitrate Versus Placebo to a High Dose Versus a Minimal Dose GnRH Antagonist Protocol on the Number of Oocytes Collected From Women That Are Poor Responders

The aim of this study is to assess the oocyte yield of infertile women with suspected or known poor ovarian reserve (POR) undergoing a GnRH antagonist protocol for IVF with Merional® starting either with a low (150 IU) or a high dose (450 IU) and adding 100mg of CC (Serophene®) in the early follicular phase of the stimulation (day 3 to 7). To date no RCT has been conducted to compare the reproductive outcome of patients with POR as defined by the ESHRE Bologna criteria after controlled ovarian hyperstimulation with HMG in an GnRH antagonist protocol using low doses versus high doses of HMG and adding CC versus placebo. We hypothesize that adding 100 mg of CC on day 3-7 to a HMG antagonist protocol will lead to an additional increment of endogenous GT thus increasing the oocytes yield after controlled ovarian stimulation due to higher endogenous gonadotropin secretion.

Study Overview

• Status: Completed
• Conditions: Female Infertility; Ovarian Insufficiency
• Intervention / Treatment: Drug: High Dose Clomiphencitrat; Drug: Low Dose Clomiphencitrat; Drug: High Dose Placebo; Drug: Low dose Placebo

• Study Type: Interventional
• Enrollment (Actual): 117
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 43 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Age: >18 years < 43 years
• BMI: ≥ 18 ≤ 32 kg/m2
• Poor responder as defined by ESHRE working group

Exclusion Criteria:

• Age < 18 und > 43 years
• Pregnancy
• Breast feeding
• Uterine conditions interfering with endometrial proliferation and embryo implantation (submucous fibroids or polyps)
• Women diagnosed with PCOS according to the Rotterdam criteria
• Hyperprolactinaemia - untreated
• Both ovaries not accessible transvaginally for oocyte pick up
• Ovarian cysts of unclear dignity
• Evidence of hydrosalpinx on ultrasound
• Clinically significant severe systemic disease that are incompatible with pregnancy
• Known or suspected hypersensitivity to the active substances (gonadotrophins, ganirelix, progesterone, clomiphencitrate)
• Untreated thyroid or adrenal disorders
• Bleeding disorders
• Cancer
• Severe renal or hepatic dysfunction
• Necessity to take medication that could influence ovarian stimulation
• History of OHSS in prior IVF cycle

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: High Dose Clomiphencitrat; 450 IU Merional® plus 100mg Serophene®	Drug: High Dose Clomiphencitrat; 100mg of clomiphencitrate(Serophene®) are added to a high dose of HMG (450 IU of Merional®) in the early follicular phase of the stimulation (day 3 to 7).
Active Comparator: Low Dose Clomiphencitrat; 150 IU Merional® plus 100mg Serophene®	Drug: Low Dose Clomiphencitrat; 100mg of clomiphencitrate(Serophene®) are added to a low dose of HMG (150 IU of Merional®) in the early follicular phase of the stimulation (day 3 to 7).
Placebo Comparator: High Dose Placebo; 450 IU Merional® plus Placebo	Drug: High Dose Placebo; Placebo is added to a high dose of HMG (450 IU of Merional®) in the early follicular phase of the stimulation (day 3 to 7).
Placebo Comparator: Low Dose Placebo; 150 IU Merional® plus Placebo	Drug: Low dose Placebo; Placebo is added to a low dose of HMG (150 IU of Merional®) in the early follicular phase of the stimulation (day 3 to 7).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
number of collected oocytes	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Implantation rate	1 year

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Rebecca E Moffat, MD, University Hospital Basel, Women's Clinic

Publications and helpful links

General Publications

• Moffat R, Hansali C, Schoetzau A, Ahler A, Gobrecht U, Beutler S, Raggi A, Sartorius G, De Geyter C. Randomised controlled trial on the effect of clomiphene citrate and gonadotropin dose on ovarian response markers and IVF outcomes in poor responders. Hum Reprod. 2021 Mar 18;36(4):987-997. doi: 10.1093/humrep/deaa336.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2013
• Primary Completion (Actual): November 14, 2017
• Study Completion (Actual): November 14, 2017

Study Registration Dates

• First Submitted: April 5, 2012
• First Submitted That Met QC Criteria: April 12, 2012
• First Posted (Estimate): April 13, 2012

Study Record Updates

• Last Update Posted (Actual): December 4, 2018
• Last Update Submitted That Met QC Criteria: December 3, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: IVF; poor ovarian response; controlled ovarian hyperstimulation; female infertility; Antagonist protocol
• Additional Relevant MeSH Terms: Infertility; Infertility, Female
• Other Study ID Numbers: CANTAPOR_2012