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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. The completion date has passed and the status has not been verified in more than two years.
Verified February 2011 by Galaxy Pharma (Pvt) Limited.
Recruitment status was:  Recruiting
Sponsor:
ClinicalTrials.gov Identifier:
NCT01058252
First Posted: January 28, 2010
Last Update Posted: February 8, 2011
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Galaxy IVF
AMERICAN IVF & PREGNANCY CENTRE - KARACHI
Fertility Care Multan
FRIENDS IVF, Faisalabad
Information provided by:
Galaxy Pharma (Pvt) Limited
  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 ]

Secondary Outcome Measures:
  • Pregnancy Rate; Cost of Treatment [ Time Frame: Every 6 months ]

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

Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 37 Years   (Adult)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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:
Ranoux C, Poirot C, Foulot H, Aubriot FX, Dubuisson JB, Chevallier O. [Intravaginal culture and embryo transfer]. Rev Fr Gynecol Obstet. 1988 Oct;83(10):637-8. French.
Ranoux C, Aubriot FX, Dubuisson JB, Cardone V, Foulot H, Poirot C, Chevallier O. A new in vitro fertilization technique: intravaginal culture. Fertil Steril. 1988 Apr;49(4):654-7.
Sterzik K, Rosenbusch B, Sasse V, Wolf A, Beier HM, Lauritzen C. A new variation of in-vitro fertilization: intravaginal culture of human oocytes and cleavage stages. Hum Reprod. 1989 Nov;4(8 Suppl):83-6.
Freude G, Artner B, Leodolter S. [Intravaginal culture--simplification of IVF]. Wien Med Wochenschr. 1990 Oct 31;140(20):498-501. German.
Sterzik K, Rosenbusch B, Sasse V, Terinde R, Wolf A, Beier HM, Lauritzen C. [Experiences and successes with intravaginal fertilization and culture of human oocytes]. Geburtshilfe Frauenheilkd. 1988 Dec;48(12):850-3. German.
Sh Tehrani Nejad E, Abediasl Z, Rashidi BH, Azimi Nekoo E, Shariat M, Amirchaghmaghi E. Comparison of the efficacy of the aromatase inhibitor letrozole and clomiphen citrate gonadotropins in controlled ovarian hyperstimulation: a prospective, simply randomized, clinical trial. J Assist Reprod Genet. 2008 May;25(5):187-90. doi: 10.1007/s10815-008-9209-2. Epub 2008 Apr 19.
Grabia A, Papier S, Pesce R, Mlayes L, Kopelman S, Sueldo C. Preliminary experience with a low-cost stimulation protocol that includes letrozole and human menopausal gonadotropins in normal responders for assisted reproductive technologies. Fertil Steril. 2006 Oct;86(4):1026-8. Epub 2006 Aug 28.
Baysoy A, Serdaroglu H, Jamal H, Karatekeli E, Ozornek H, Attar E. Letrozole versus human menopausal gonadotrophin in women undergoing intrauterine insemination. Reprod Biomed Online. 2006 Aug;13(2):208-12.
Jee BC, Ku SY, Suh CS, Kim KC, Lee WD, Kim SH. Use of letrozole versus clomiphene citrate combined with gonadotropins in intrauterine insemination cycles: a pilot study. Fertil Steril. 2006 Jun;85(6):1774-7. Epub 2006 May 4.
Garcia-Velasco JA, Moreno L, Pacheco A, Guillén A, Duque L, Requena A, Pellicer A. The aromatase inhibitor letrozole increases the concentration of intraovarian androgens and improves in vitro fertilization outcome in low responder patients: a pilot study. Fertil Steril. 2005 Jul;84(1):82-7.
Verpoest WM, Kolibianakis E, Papanikolaou E, Smitz J, Van Steirteghem A, Devroey P. Aromatase inhibitors in ovarian stimulation for IVF/ICSI: a pilot study. Reprod Biomed Online. 2006 Aug;13(2):166-72.
Ozmen B, Sönmezer M, Atabekoglu CS, Olmus H. Use of aromatase inhibitors in poor-responder patients receiving GnRH antagonist protocols. Reprod Biomed Online. 2009 Oct;19(4):478-85.
Goswami SK, Das T, Chattopadhyay R, Sawhney V, Kumar J, Chaudhury K, Chakravarty BN, Kabir SN. A randomized single-blind controlled trial of letrozole as a low-cost IVF protocol in women with poor ovarian response: a preliminary report. Hum Reprod. 2004 Sep;19(9):2031-5. Epub 2004 Jun 24.
Kadoch IJ, Al-Khaduri M, Phillips SJ, Lapensée L, Couturier B, Hemmings R, Bissonnette F. Spontaneous ovulation rate before oocyte retrieval in modified natural cycle IVF with and without indomethacin. Reprod Biomed Online. 2008 Feb;16(2):245-9.
Janssens RM, Lambalk CB, Vermeiden JP, Schats R, Schoemaker J. In-vitro fertilization in a spontaneous cycle: easy, cheap and realistic. Hum Reprod. 2000 Feb;15(2):314-8.
Bernabeu R, Roca M, Torres A, Ten J. Indomethacin effect on implantation rates in oocyte recipients. Hum Reprod. 2006 Feb;21(2):364-9. Epub 2005 Nov 10.
Hewitt J. Intravaginal culture: present and potential uses. Br J Hosp Med. 1990 Sep;44(3):182, 184-5, 188. Review.

Responsible Party: Saif Ur Rehman, Project Director, Galaxy IVF (UK) Limited
ClinicalTrials.gov Identifier: NCT01058252     History of Changes
Other Study ID Numbers: GIVF-1001
First Submitted: January 27, 2010
First Posted: January 28, 2010
Last Update Posted: February 8, 2011
Last Verified: February 2011

Additional relevant MeSH terms:
Infertility
Genital Diseases, Male
Genital Diseases, Female
Letrozole
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs


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