Minimal Stimulation Protocol Using Aromek(Letrozole) and Follitrope(recFSH) Combined With INVOCell-Low Cost IVF (MSP-IVC)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2011 by Galaxy Pharma (Pvt) Limited.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Galaxy IVF
AMERICAN IVF & PREGNANCY CENTRE - KARACHI
Fertility Care Multan
FRIENDS IVF, Faisalabad
Information provided by:
Galaxy Pharma (Pvt) Limited
ClinicalTrials.gov Identifier:
NCT01058252
First received: January 27, 2010
Last updated: February 6, 2011
Last verified: February 2011
  Purpose

The purpose of this study to evaluate a low cost minimal stimulation protocol combined with Intravaginal Culturing, to make IVF affordable and available across the large infertile/subfertile population


Condition Intervention
Primary Infertility
Secondary Infertility
Low Responders
Mild to Moderate Male Factor Infertility
Drug: Letrozole 2.5 mg, recFSH 75 IU
Procedure: STEP-3: LH Suppression & Monitoring
Procedure: STEP-4: HCG Timing
Procedure: STEP-5: OPU, ET, Cancellation
Procedure: INVOCell (Intravaginal Culturing)

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Scientific & Clinical Review of Minimal Stimulation Protocol Using AROMEK (Letrozole) and Follitrope (Recombinant FSH)Combined With INVOCell(Intravaginal Culturing) - Effectiveness as Low Cost IVF

Resource links provided by NLM:


Further study details as provided by Galaxy Pharma (Pvt) Limited:

Primary Outcome Measures:
  • Number of Follicles >15 mm on the day of HCG; Number of Oocytes aspirated; Fertilisation Rate [ Time Frame: Quarterly ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pregnancy Rate; Cost of Treatment [ Time Frame: Every 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 100
Study Start Date: February 2011
Estimated Study Completion Date: February 2012
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Letrozole, recFSH, IVC, Monitoring
Infertile couple following MSP with IVC
Drug: Letrozole 2.5 mg, recFSH 75 IU

OVARIAN STIMULATION:

In previous cycles, cycle length and ovulatory status must be assessed and documented.

STEP 1: ANOVULATION by ORAL CONTRACEPTION

  • Place patients on monophasic low dose of oral contraceptive pills (OCP) such as Marvelon (Organon, 0.03 mg) continuously for 21 days, 22 days but no more.
  • Before stopping the oral contraceptive pills, perform an ultrasound to check for the absence of cysts (no cyst > 10 mm).
  • Give estradiol (2mg, 3 times a day) for 3 days from D21 or D22 and wait for bleeding.

STEP 2: STIMULATION and MONITORING Day one of the cycle equals the first day of bleeding (not spotting).

  • On Day 3 (D3), start letrozol 2.5mg (AROMEK) for 5 days (D7). LetrozolE can be pushed for 2 more days.
  • Start hMG or FSH (75 IU a day) on Day 3 like LetrozolE and continue for 5 to 7 days without increasing the dose. The dose of hMG OR FSH can be increased to 150 IU a day if low responder.
Other Names:
  • Aromek (Letrozole 2.5 mg);
  • Follitrope (Recombinent FSH - 75 IU)
  • IVF-C 5000 IU (HCG)
  • Ova-Surge (Urinary LH Surge Kit)
  • Indomethacin 50 mg
Procedure: STEP-3: LH Suppression & Monitoring

Baseline Day-2 Ultrasound to estimate antral follicles; Follow-up TVS scans on Day- 5,6,7,8 and 9 of the stimulated cycle. Ideally the lead follicle should be 18 mm on or around day 10 of the cycle.

• When the leading follicle reaches 14 to15 mm (D8 or D9), give Indomethacine (50 mg, 3 times a day) until the evening preceding the egg retrieval. The Indomethacine will prevent a premature ovulation.

The endometrium should be minimum 8 mm on the day of HCG (IVF-C 5000 IU x 2)

No need of LH testing, or E2 testsing during the stimulated cycle.

Procedure: STEP-4: HCG Timing

IVF-C (HCG 10000 IU) shall be injected to trigger the ovulation, when any of the following occur:

  • E2 level is over 150 pg/ml/per mature follicle (> 15 mm)
  • Domminent follicle is greater than 18 mm in mean diameter
  • LH Remains as Baseline, OR
  • The day when Urinary LH Surge is positive
Other Name: IVF-C 5000 IU
Procedure: STEP-5: OPU, ET, Cancellation

Ultrasound guided Ovum Pick-Up is performed 34-36 hours after IVF-C (HCG 10000 IU) injection.

Embryo Transfer is performed after 48-72 hours of incubation at 4-8 cell stage.

Maximum of 2 embryos are transferred, using ultrasound guided transfer.

Cancellation Criteria:

  • Poor patient compliance
  • Premature Ovulation
  • Premature LH Surge
  • Endometrium < 7 mm
  • Poor Follicular Development
  • E2 Level > 2,500 pg/ml
Other Names:
  • Ovum Pick-Up
  • Embryo Transfer
  • Ultrasound Guided
Procedure: INVOCell (Intravaginal Culturing)
Sperm preparation through Swim-Up or Gradient is performed 1 hour prior to the oocyte retrieval; Fill the device without air bubble. Only 30000 motile spermatozoa are added into the device; After follicle aspiration, oocyte(s) are identified in the follicular fluid and immediately placed into the device; The device is closed, placed into a protective outer rigid shell and then positioned into the vaginal cavity for 2 to 3 days; No activity restriction is required for the patient, except baths. After 2 or 3 days of incubation, the retention system and the device are removed from the vagina in sterile environment. The device is opened and the contents are observed in a sterile environment under microscope to find the embryos. The two best quality embryos are loaded into embryo transfer catheter and transferred immediately unto the uterine cavity using aseptic techniques.
Other Names:
  • INVOCell
  • Diaphragm (Retention Device)

Detailed Description:

In routine ART procedures for IVF, ovarian stimulation is performed using down regulation with GNRH Agonist combined with high daily FSH doses followed with ovulation induction with HCG 10000 IU, ovum pick-up 34-36 hours after HCG injection and embryo transfer on day 2, 3 or 5.

In routine ART procedure for IVF, embryology is done in very high tech lab, contamination free environment, which also exclude VOC, high quality CO2 Incubators, laminar flow with heated table top, high magnification stereo microscope along with equipments for maintaining quality control, with a highly trained embryologist. The primary reason is we need to create a womb like environment in the embryology lab as eggs, and mainly fertilised embryos are going to spend minimum 2 or 3 and in case blastocyst 5 days in this lab.

In recent years, various studies have been published identifying various minimal stimulation protocols for IVF, and also another variation of IVF where rather than using CO2 Incubator for culturing, vaginal cavity of the female partner is used for incubation using a specially designed capsule which have walls permeable to vaginal pCO2 and O2. Oocytes are retrieved by the physician and handed over to basic embryologist to identify and grade oocytes and washed sperms are placed in a embryo toxic tested, sterile, individual single use capsule (INVOCell) and placed in vaginal cavity using diaphragm, patient goes back to home with some instructions for care, on day 2 patient comes back to the IVF Clinic and physician gets the capsule out and hands over to the basic embryologist trained on INVOCell to identify embryos and grade them, further loading of embryos on ET Catheter.

  Eligibility

Ages Eligible for Study:   20 Years to 37 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

IVF Network Centers across the country, selecting patients meeting inclusion criteria.

Criteria

Inclusion Criteria:

  • Tubal factor without Hydrosalpinx
  • Unexplained infertility with unsuccessful attempts in achieving pregnancy through timed intercourse or IUI
  • Boarder line male factor infertility
  • Sperm DNA Fragmentation < 30%
  • Normal Uterine Cavity
  • Normal baseline ultrasound with adequate number of primary follicles present
  • Normal FSH and E2 on Day 3
  • Age of the female is < 35 years old

Exclusion Criteria:

  • If previous IVF or INVO attempts resulted in failed fertilisation
  • Male partner who has difficulty in producing semen sample
  • Very low sperm count, very low percentage of sperm motility and morphology
  • Sperm DNA Fragmentation > 30%
  • Age of female patient > 37 years
  • Borderline or elevated E2 or FSH on day 3 or failed CCCT or low blood inhibin levels
  • Poor ovarian response
  • Hydrosalpinx
  • Anatomic difficulties in reaching ovaries for oocyte retrieval
  • Cervical stenosis, making embryo transfer difficult
  • Uterine abnormalities or deformities
  • Obesity
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01058252

Contacts
Contact: Prof. Claude Ranoux, MD 978 878-9505 clauderanoux@invobioscience.com
Contact: Saif Ur Rehman 0092 323 2440710 saifrehman@galaxyivf.com

Locations
Pakistan
Friends Ivf Recruiting
Faisalabad, Punjab, Pakistan
Contact: Dr. Samina Khalid, MCPS, FCPS    0092 300 8664227      
Sub-Investigator: Dr. Samina Khalid, MCPS, FCPS         
Fertility Care Multan Recruiting
Multan, Punjab, Pakistan
Contact: Prof. Samee Akhtar    0092 300 8637070      
Principal Investigator: Prof. Samee Akhtar, FCPS, FRCOG         
Sub-Investigator: Talha Mabood Paracha, Embryologyst         
Galaxy IVF Limited Recruiting
Karachi, Sindh, Pakistan, 75300
Contact: Saif Ur Rehman    0092 323 2440710    saifrehman@galaxyivf.com   
Contact: Talha Mabood Paracha, Embryologyst         
Sub-Investigator: Talha Mabood Paracha, Embryologyst         
American IVF & Pregnancy Center Recruiting
Karachi, Sindh, Pakistan
Contact: Dr. Asma Munir, MCPS, FCPS         
Contact: Pervaiz Masood Khan         
Principal Investigator: Prof. Claude Ranoux, MS, MD         
Sponsors and Collaborators
Galaxy Pharma (Pvt) Limited
Galaxy IVF
AMERICAN IVF & PREGNANCY CENTRE - KARACHI
Fertility Care Multan
FRIENDS IVF, Faisalabad
Investigators
Study Chair: Prof. Claude Ranoux, MD INVOBioscience, USA
  More Information

Publications:

Responsible Party: Saif Ur Rehman, Project Director, Galaxy IVF (UK) Limited
ClinicalTrials.gov Identifier: NCT01058252     History of Changes
Other Study ID Numbers: GIVF-1001
Study First Received: January 27, 2010
Last Updated: February 6, 2011
Health Authority: Pakistan: Research Ethics Committee

Additional relevant MeSH terms:
Infertility
Genital Diseases, Male
Genital Diseases, Female
Indomethacin
Letrozole
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Cardiovascular Agents
Gout Suppressants
Tocolytic Agents
Reproductive Control Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents
Antineoplastic Agents
Aromatase Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014