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

NCT01058252 | Unknown FDA Device

• 1 other identifier: GIVF-SRM 1001
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Primary Infertility; Secondary Infertility; Low Responders; Mild to Moderate Male Factor Infertility

Outcome Measures

Primary Outcomes (1)

• Number of Follicles >18 mm on the day of HCG; Number of Oocytes aspirated; Fertilisation Rate

  Quarterly

Secondary Outcomes (1)

• Pregnancy Rate; Cost of Treatment

  Every 6 months

Study Arms (1)

Letrozole, recFSH, INVOCell, Monitoring

Infertile couple following MSP with INVO IVF

Combination Product: INVOCell, 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)

Interventions

INVOCell, Letrozole 2.5 mg, recFSH 75 IU COMBINATION_PRODUCT

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.

Also known as: Aromek (Letrozole 2.5 mg);, Follitrope (Recombinent FSH - 75 IU), IVF-C 5000 IU (HCG), Ova-Surge (Urinary LH Surge Kit), Indomethacin 50 mg

Letrozole, recFSH, INVOCell, Monitoring

STEP-3: LH Suppression & Monitoring PROCEDURE

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.

Letrozole, recFSH, INVOCell, Monitoring

STEP-4: HCG Timing PROCEDURE

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

Also known as: IVF-C 5000 IU

Letrozole, recFSH, INVOCell, Monitoring

STEP-5: OPU, ET, Cancellation PROCEDURE

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

Also known as: Ovum Pick-Up, Embryo Transfer, Ultrasound Guided

Letrozole, recFSH, INVOCell, Monitoring

INVOCell (Intravaginal Culturing) PROCEDURE

Sperm preparation through Swim-Up or Gradient is performed 1 hour prior to the oocyte retrieval; Fill the device without air bubble. Only 100000 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.

Also known as: INVOCell, Diaphragm (Retention Device)

Letrozole, recFSH, INVOCell, Monitoring

Eligibility Criteria

• Age: 20 Years - 37 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Galaxy Pharma (Pvt) Limited: lead
• Ova IVF & Reproductive Health Clinics, Karachi: collaborator

Study Sites (2)

Lady Wallington Hospital

Lahore, Punjab Province, Pakistan

RECRUITING

Ova IVF & Reproductive Health Clinics

Karachi, Sindh, 75300, Pakistan

RECRUITING

Related Publications (23)

• Hewitt J. Intravaginal culture: present and potential uses. Br J Hosp Med. 1990 Sep;44(3):182, 184-5, 188.

  PMID: 2257400 BACKGROUND

• 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.

  PMID: 3201055 RESULT

• 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. doi: 10.1016/s0015-0282(16)59835-5.

  PMID: 3350160 RESULT

• 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. doi: 10.1093/humrep/4.suppl_1.83.

  PMID: 2613877 RESULT

• Freude G, Artner B, Leodolter S. [Intravaginal culture--simplification of IVF]. Wien Med Wochenschr. 1990 Oct 31;140(20):498-501. German.

  PMID: 2264352 RESULT

• 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. doi: 10.1055/s-2008-1026639. German.

  PMID: 3234716 RESULT

• 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.

  PMID: 18427974 RESULT

• 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. doi: 10.1016/j.fertnstert.2006.03.034. Epub 2006 Aug 28.

  PMID: 16935285 RESULT

• 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. doi: 10.1016/s1472-6483(10)60617-7.

  PMID: 16895634 RESULT

• 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. doi: 10.1016/j.fertnstert.2006.02.070. Epub 2006 May 4.

  PMID: 16677640 RESULT

• Garcia-Velasco JA, Moreno L, Pacheco A, Guillen 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. doi: 10.1016/j.fertnstert.2005.01.117.

  PMID: 16009161 RESULT

• 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. doi: 10.1016/s1472-6483(10)60611-6.

  PMID: 16895628 RESULT

• Ozmen B, Sonmezer 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. doi: 10.1016/j.rbmo.2009.05.007.

  PMID: 19909587 RESULT

• 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. doi: 10.1093/humrep/deh359. Epub 2004 Jun 24.

  PMID: 15217999 RESULT

• Kadoch IJ, Al-Khaduri M, Phillips SJ, Lapensee 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. doi: 10.1016/s1472-6483(10)60581-0.

  PMID: 18284881 RESULT

• 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. doi: 10.1093/humrep/15.2.314.

  PMID: 10655301 RESULT

• Bernabeu R, Roca M, Torres A, Ten J. Indomethacin effect on implantation rates in oocyte recipients. Hum Reprod. 2006 Feb;21(2):364-9. doi: 10.1093/humrep/dei343. Epub 2005 Nov 10.

  PMID: 16284067 RESULT

• Khan M, Zafar S, Syed S. Successful intravaginal culture of human embryos for the first time in Pakistan--an experience at the Sindh Institute of Reproductive Medicine, Karachi. J Pak Med Assoc. 2013 May;63(5):630-2.

  PMID: 23757995 RESULT

• Lucena E, Saa AM, Navarro DE, Pulido C, Lombana O, Moran A. INVO procedure: minimally invasive IVF as an alternative treatment option for infertile couples. ScientificWorldJournal. 2012;2012:571596. doi: 10.1100/2012/571596. Epub 2012 May 2.

  PMID: 22645435 RESULT

• Doody KJ, Broome EJ, Doody KM. Comparing blastocyst quality and live birth rates of intravaginal culture using INVOcell to traditional in vitro incubation in a randomized open-label prospective controlled trial. J Assist Reprod Genet. 2016 Apr;33(4):495-500. doi: 10.1007/s10815-016-0661-0. Epub 2016 Feb 3.

  PMID: 26843390 RESULT

• Babcock Gilbert S, Polotsky AJ. Vaginal culture for IVF allows two mothers to carry the same pregnancy: Is more always better? Case Rep Womens Health. 2019 Jan 26;21:e00099. doi: 10.1016/j.crwh.2019.e00099. eCollection 2019 Jan.

  PMID: 30733926 RESULT

• Garcia-Ferreyra J, Hilario R, Luna D, Villegas L, Romero R, Zavala P, Duenas-Chacon J. In Vivo Culture System Using the INVOcell Device Shows Similar Pregnancy and Implantation Rates to Those Obtained from In Vivo Culture System in ICSI Procedures. Clin Med Insights Reprod Health. 2015 Jun 10;9:7-11. doi: 10.4137/CMRH.S25494. eCollection 2015.

  PMID: 26085790 RESULT

• Mitri F, Esfandiari N, Coogan-Prewer J, Chang P, Bentov Y, McNaught J, Klement AH, Casper RF. A pilot study to evaluate a device for the intravaginal culture of embryos. Reprod Biomed Online. 2015 Dec;31(6):732-8. doi: 10.1016/j.rbmo.2015.09.005. Epub 2015 Sep 18.

  PMID: 26602106 RESULT

Related Links

• Real-world experience with intravaginal culture using INVOCELL: an alternative model for infertility treatment

MeSH Terms

Interventions

Letrozole; Indomethacin; Embryo Transfer; Contraceptive Devices, Female

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Reproductive Techniques, Assisted; Reproductive Techniques; Therapeutics; Investigative Techniques; Contraceptive Devices; Equipment and Supplies

Study Officials

• Dr Gul Rana, MBBS

  Ova IVF & Reproductive Health Clinics

  STUDY DIRECTOR

Central Study Contacts

Dr Gul Rana, MBBS

CONTACT

+923353039246; gulrana8@gmail.com

Saif Ur Rehman, MS

CONTACT

0092 323 2440710; saifrehman@ovaivf-rhc.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2010
• First Posted: January 28, 2010
• Study Start: May 1, 2021
• Primary Completion: December 1, 2021
• Study Completion: March 1, 2022
• Last Updated: March 24, 2021

Record last verified: 2021-03

Locations

PA (2)