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Fertilization in VitroNCT03527823

The Comparison of Granulosa Cell Apoptosis Rates With or Without Luteinizing Hormone Administration in Poor Responders.

An observational study of Fertilization in Vitro, run by Sebnem Alanya Tosun at 1 site in Turkey (Türkiye).

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

In Zeynep Kamil Women and Children's Education and Research Hospital which is a tertiary referral hospital, the investigators perform microdose flare-up gonadotropin-releasing hormone (GNRH) analogue or GNRH antagonist protocol to the poor responders. Read more about this study

Who is it for?
Ages 18 to 49 years, women onlyHealthy volunteers can take part
Conditions the study is for
Fertilization in Vitro
How many people
31 participants
Where
1 siteTurkey (Türkiye)
Study dates
17 Oct 2018to 10 Jan 2019
How long will I take part?
1 Month
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 49 years
  • Women only
  • Healthy volunteers accepted
  • Adult

Study population: 18-49 aged females who undergoes IVF treatment and who are defined as poor responders

Who may be able to join

  • 18-49 aged female
  • poor ovarian responders
  • undergoing treatment for primary/secondary infertility

Who cannot join

  • endocrinologic or metabolic disorders

Trial locations and contacts

1 site in 1 country.

Turkey (Türkiye)1 site
  • Sebnem Alanya Tosun

    Giresun

Other trials in Turkey (Türkiye)

About this study

Official title: The Comparison of Granulosa Cell Apoptosis Rates on Microdose Flare up GnRH Analog Protocol Versus Luteinizing Hormone Administrated Microdose Flare up GnRH Analog Protocol in Poor Ovarian Responders Undergoing in Vitro Fertilization.

In Zeynep Kamil Women and Children's Education and Research Hospital which is a tertiary referral hospital, the investigators perform microdose flare-up gonadotropin-releasing hormone (GNRH) analogue or GNRH antagonist protocol to the poor responders. The investigators may or may not supplement luteinizing hormone (LH). Human chorionic gonadotropin (hCG) triggering is performed when at least 2 follicles diameter are above 17 mm and the serum estradiol level is above 500 pg / ml. 36 hours after hCG, ovarian aspiration is performed by the guidance of transvaginal ultrasound. Normally after oocyte separation process, the remaining follicle aspiration fluid is destroyed.

n the present study, the follicle aspiration fluid is planned to be used with the patient's permission. The investigators are going to examine the granulosa cell apoptosis rate by using annexin-5 antibody in both groups 1 (LH added) and 2 (without LH).

Read more

For this purpose, a total of 40 volunteer patients are planned to involve, the groups are designed as 20 LH added and 20 LH added women.

In the present study, the investigators hypothesis that the rates of granulosa cell apoptosis in poor responders may be different between the group 1 (with LH) and group 2 (without LH), this will lead to IVF therapy in the near future.

Read the detailed description

The supplementation of human menopausal gonadotropin (HMG) in terms of luteinizing hormone (LH) support in controlled ovarian stimulation (COS) is a controversial issue. Follicle stimulating hormone (FSH) and LH are required for ovarian steroidogenesis in anovulatory women with gonadotropin deficiency according to the two cell-two gonadotropin hypothesis. LH supplementation is needed to ensure adequate follicular estradiol (E2) production during the follicular phase, completion of oocyte maturation and development in the endometrium. Despite, the need for LH for ovarian stimulation in normogonadotropic women is controversial. Additional LH supplementation during stimulation with FSH may provide an advantage in increasing follicle development and thus may be shortening the duration of treatment. It has been suggested that the change of gonadotropins from FSH to LH in the presence of ovarian stimulation is beneficial in the development of a more homogeneous follicular cohort [1] [2]. However, contrary opinions have reported that LH supplementation does not bring any additional benefit [3].

In recent years, studies have been done to investigate the utility of the addition of LH as well as FSH to the cycle outcome. In a Cochrane review, the combination of recombinant follicle stimulating hormone (r-FSH) and recombinant luteinizing hormone (r-LH) administration in in vitro fertilization/intracytoplasmic sperm injection (IVF / ICSI) cycles compared to only r-FSH cycles in 14 randomized controlled trials [4]. When r-LH was added, there was no statistical difference in terms of pregnancy outcomes. However, due to the small size of the work, the net result was not achieved. The other study supported the treatment of rFSH alone, while the addition of r-LH was found to be beneficial only in one of the studies [5, 6] . As a result, there is no significant difference in live birth rates.

However, the studies in only poor responders showed a significant increase in pregnancy rates with the addition of r-LH [5, 7]. In contrast, recently Bosch et al. reported that the addition of r-LH in the 36-39 age group of patients with GnRH antagonist protocol benefit from LH support, while patients under the age of 36 do not [8]. In conclusion, there is no consensus to administrate r-LH to the protocols of poor responders. Our hypothesis is LH administration may decrease granulosa apoptosis rate in follicular fluids and may be beneficial to poor responders and over age of 35.

In Zeynep Kamil Women and Children's Education and Research Hospital where the data of study patients is going to be collected, the investigators are applying microdose flare-up GNRH analogue or GNRH antagonist protocol to the poor responders. The investigators may or may not supplement LH. hCG is performed when at least 2 follicles are 17 mm and the serum estradiol level is above 500 pg / ml. 36 hours after hCG, ovarian aspiration is performed by the guidance of transvaginal ultrasound. Normally after oocyte separation process, the remaining follicle aspiration fluid is destroyed.

The follicle aspiration fluid is planned to be used within the permission of the patient in the present study. The investigators are going to examine the granulosa cell apoptosis rate with using annexin-5 antibody in group 1 (LH added) and group 2 (without LH).

For this purpose, a total of 40 volunteer patients are planned to have 20 LH added and 20 LH added patient groups.

Statistical analysis is going to be performed using SPSS 11 program. p <0.05 will be considered significant.

In the present study, the investigators hypothesis that comparing the rates of granulosa cell apoptosis in poor responders as two different groups (with and without addition of LH) will lead to IVF therapy in the near future.

Keywords
Fertilization in Vitro, Granulosa Cells, Apoptosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT03527823
Study groupRoleWhat they receive
LH supplementationluteinizing hormone administrated microdose flare up GnRH analog protocol in poor ovarian responders undergoing in vitro fertilization.
without LH supplementationmicrodose flare up GnRH analog protocol in poor ovarian responders

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. the comparison of granulosa cell apoptosis rate with or without LH supplementation in poor responders

    the investigators hypothesized that granulosa cell apoptosis rate on luteinizing hormone supplemented microdose flare up GnRH analog protocol in poor ovarian responders undergoing in vitro fertilization would be lower than not administered protocol

    Measured: June 2018-August 2018

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 May 2018
  2. Study start17 Oct 2018
  3. Primary completion1 Dec 2018
  4. Study completion10 Jan 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
31 participants (actual)
Target duration
1 Month
IDs, dates and publications
ClinicalTrials.gov ID
NCT03527823
Sponsor's protocol ID
GranulosaApoptosis
Other IDs
123
Status last verified
Jun 2020
First submitted
25 Apr 2018
Last updated
22 Jun 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Bosch E, Labarta E, Crespo J, Simon C, Remohi J, Pellicer A. Impact of luteinizing hormone administration on gonadotropin-releasing hormone antagonist cycles: an age-adjusted analysis. Fertil Steril. 2011 Mar 1;95(3):1031-6. doi: 10.1016/j.fertnstert.2010.10.021. Epub 2010 Nov 10.

    PubMed 21067717
  • Ferraretti AP, Gianaroli L, Magli MC, D'angelo A, Farfalli V, Montanaro N. Exogenous luteinizing hormone in controlled ovarian hyperstimulation for assisted reproduction techniques. Fertil Steril. 2004 Dec;82(6):1521-6. doi: 10.1016/j.fertnstert.2004.06.041.

    PubMed 15589853
  • Kaleli S, Yanikkaya-Demirel G, Erel CT, Senturk LM, Topcuoglu A, Irez T. High rate of aneuploidy in luteinized granulosa cells obtained from follicular fluid in women who underwent controlled ovarian hyperstimulation. Fertil Steril. 2005 Sep;84(3):802-4. doi: 10.1016/j.fertnstert.2005.02.040.

    PubMed 16169431
  • Sullivan MW, Stewart-Akers A, Krasnow JS, Berga SL, Zeleznik AJ. Ovarian responses in women to recombinant follicle-stimulating hormone and luteinizing hormone (LH): a role for LH in the final stages of follicular maturation. J Clin Endocrinol Metab. 1999 Jan;84(1):228-32. doi: 10.1210/jcem.84.1.5389.

    PubMed 9920089
  • Filicori M, Cognigni GE, Samara A, Melappioni S, Perri T, Cantelli B, Parmegiani L, Pelusi G, DeAloysio D. The use of LH activity to drive folliculogenesis: exploring uncharted territories in ovulation induction. Hum Reprod Update. 2002 Nov-Dec;8(6):543-57. doi: 10.1093/humupd/8.6.543.

    PubMed 12498424
  • Balasch J, Vidal E, Penarrubia J, Casamitjana R, Carmona F, Creus M, Fabregues F, Vanrell JA. Suppression of LH during ovarian stimulation: analysing threshold values and effects on ovarian response and the outcome of assisted reproduction in down-regulated women stimulated with recombinant FSH. Hum Reprod. 2001 Aug;16(8):1636-43. doi: 10.1093/humrep/16.8.1636.

    PubMed 11473955
  • Mochtar MH, Van der Veen, Ziech M, van Wely M. Recombinant Luteinizing Hormone (rLH) for controlled ovarian hyperstimulation in assisted reproductive cycles. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD005070. doi: 10.1002/14651858.CD005070.pub2.

    PubMed 17443569
  • Tarlatzis B, Tavmergen E, Szamatowicz M, Barash A, Amit A, Levitas E, Shoham Z. The use of recombinant human LH (lutropin alfa) in the late stimulation phase of assisted reproduction cycles: a double-blind, randomized, prospective study. Hum Reprod. 2006 Jan;21(1):90-4. doi: 10.1093/humrep/dei293. Epub 2005 Sep 19.

    PubMed 16172149
  • De Placido G, Alviggi C, Perino A, Strina I, Lisi F, Fasolino A, De Palo R, Ranieri A, Colacurci N, Mollo A; Italian Collaborative Group on Recombinant Human Luteinizing Hormone. Recombinant human LH supplementation versus recombinant human FSH (rFSH) step-up protocol during controlled ovarian stimulation in normogonadotrophic women with initial inadequate ovarian response to rFSH. A multicentre, prospective, randomized controlled trial. Hum Reprod. 2005 Feb;20(2):390-6. doi: 10.1093/humrep/deh625. Epub 2004 Dec 2.

    PubMed 15576390

Questions about this trial

What is this clinical trial studying?

An observational study of Fertilization in Vitro, run by Sebnem Alanya Tosun at 1 site in Turkey (Türkiye).

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

the comparison of granulosa cell apoptosis rate with or without LH supplementation in poor responders (time frame: June 2018-August 2018). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03527823, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2020.

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