IVFNCT01790282
Is Adding E2 to P4 Luteal Support In High Responder Long Gn-RH Agonist ICSI Cycles Detrimental to Outcome? RCT
A study testing estradiol plus progesterone 100 mg IM injection and Progesterone IM of 100 mg in people with IVF and Infertility, run by Mansoura Integrated Fertility Center at 1 site in Egypt.
Trial summary
Study if supporting luteal phase of high responder (high egg production or high Estradiol level) long Gn_Rh agonist protocol ICSI/IVF cycle by combined Estradiol and progesterone impairs or improves outcome in terms of pregnancy and implanation rates. Read more about this study
- Who is it for?
- Ages 18 to 39 years, women only
- Conditions the study is for
- IVF, Infertility
- What is being tested?
- estradiol plus progesterone 100 mg IM injection and Progesterone IM of 100 mg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 220 participants
- Where
- 1 siteEgypt
- Study dates
- Mar 2013to Mar 2015
- Phase
- Interventional
- 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 39 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- age<40 years,
- first ICSI cycle,
- third day FSH< 10 mIU/mL,
- serum E2 level on day of hCG administration <4,000 pg/mL,
- number of ova obtained >15
Who cannot join
- age 40 years or more,
- basal FSH 10 mIU/mL or more ,
- eggs retrieved 15 or less ,
- E2 level on day of hCG administration 4000 or more pg/ mL or more,
- repeat ICSI , need for PGD, presence of myoma , hydrosalpinx (unless disconnected)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Is E2 Luteal Support in High Responder Long Gn-RH Agonist ICSI Cycles Detrimental to Cycle Outcome ? A Randomized Clinical Trial
Study if supporting luteal phase of high responder (high egg production or high Estradiol level) long Gn_Rh agonist protocol ICSI/IVF cycle by combined Estradiol and progesterone impairs or improves outcome in terms of pregnancy and implanation rates.
Read the detailed description
The role of estradiol (E2) luteal support is still debated after more than a decade of use. Two recent met analyses (Gelbaya et al 2008) \&(Jee et al 2010)( ) has shown that the addition of E2 to P4 for luteal phase support in IVF/ICSI cycles has no beneficial effect on pregnancy rates. However they commented that the data in the literature are, limited and heterogeneous, precluding the extraction of clear and definite conclusions. Previous met analysis ( Pritts and Atwood 2002 ) and an update (Fatemi et al 2007 ) and subsequent randomized trials ( Ghanem et al 2009 , Var et al 2011 ) reported beneficial effects of adding E2 to luteal P4 support. Recent retrospective studies have shown that high response in terms of excess egg production ( >15 . ) and or high E2 (Chen et al 2007,Kyrou et al 2009, Sunkara 2011 ) are detrimental to cycle outcome. This prospective randomized trial aims to study whether adding E2 to P4 luteal support in high ovarian responders is detrimental to cycle outcome or not
--------------- Gelbaya TA, KyrgiouM, Tsoumpou I, Nardo LG. The use of estradiol for luteal phase support in in vitro fertilization/intracytoplasmic sperminjec- tion cycles: a systematic review and meta-analysis. Fertil Steril 2008;90: 2116-25.
Jee BC, Suh CS, Kim SH, Kim YB, Moon SY. Effects of estradiol supplementation during the luteal phase of in vitro fertilization cycles: a meta-analysis Fertil Steril. 2010 Feb;93(2):428-36
Pritts EA, Atwood AK. Luteal phase support in infertility treatment: a meta-analysis of randomized trials. Hum Reprod 2002;17:2287-99 Fatemi HM, Popovic-Todorovic B, Papanikolaou E, Donoso P,Devroey P. An update of luteal phase support in stimulated IVF cycles.Hum Reprod Update 2007;13:581.
- Ghanem M E., Ehab E. Sadek, Elboghdady L. A.. Helal A S, Gamal Anas, Eldiasty A Bakre N I., Houssen M .The effect of luteal phase support protocol on cycle outcome and luteal phase hormone profile in long agonist protocol intracytoplasmic sperm injection cycles: a randomized clinical trial , Fertility and Sterility 2009 92: 486-493
Var T, Tonguc EA, Doğanay M, Gulerman C, Gungor T, Mollamahmutoglu L. A comparison of the effects of three different luteal phase support protocols on in vitro fertilization outcomes: a randomized clinical trial. Fertil Steril. 2011 Mar 1;95(3):985-9.
van der Gaast, Eijkemans JB, de Boer EJ, Burger CW , van Leeuwen FE, Fauser BCJM , and Macklon NS Optimum number of oocytes for a successful first IVF treatment cycle Reproductive BioMedicine Online 2006 ; 13: 476-480
Sunkara SK, Rittenberg V, Raine-Fenning N, Bhattacharya S, Zamora J, Coomarasamy A. Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. Hum Reprod 2011; 26: 1768-1774
Chen QJ, Sun XX, Li L, Gao XH, Wu Y, Gemzell-Danielsson K, Cheng LN Effects of ovarian high response on implantation and pregnancy outcome during controlled ovarian hyperstimulation (with GnRH agonist and rFSH). Acta Obstet Gynecol Scand. 2007;86:849-54 Kyrou D., Popovic-Todorovic B., Fatemi H.M1, Bourgain C, Haentjens P., Van Landuyt L., and. Devroey P Does the estradiol level on the day of human chorionic gonadotrophin administration have an impact on pregnancy rates in patients treated with rec-FSH/GnRH antagonist? Hum Reprod 2009, 2902-2909,
- Conditions
- IVF, Infertility
- Being tested
- estradiol plus progesterone 100 mg IM injection, Progesterone IM of 100 mg
- Keywords
- luteal support, high responder, ICSI, cycle outcome
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
estradiol plus progesterone 100 mg IM injectionDrug
Also called estradiole valerate 2mg,, Prontogest 100 mg
estradile valaerate 2mg plus progesterone 100 mg/day support arm :E2 valerate 2mg three times /day are given to the arm cases plus P4 100 IM/day for 14 days starting on day of ovum pickup and single IM injection of 0.1 mg decapeptyl on day of ET
Progesterone IM of 100 mgDrug
Also called prontogest 100 mg ampoles
Starting on day of ovum pickup ICSI cases are given prontogest 100 mg IM /day plus single dose dose of treptorline 0.1mg is given sc on day of embryo transfer
| Study group | Role | What they receive |
|---|---|---|
| estradiole - progesterone arm | Experimental | Cases are given estradiole valerate 2mg 3 times /day from day of ovum pick up until the time of pregnancy test two weeks together with daily IM injection of 100 progesterone starting . Single intramuscular 0.1 mg decapeptyl are given on day of transfer Receives: Drug: estradiol plus progesterone 100 mg IM injection; Drug: Progesterone IM of 100 mg |
| Progesterone only arm | Active comparator | Patient are given 100 mg progesterone daily starting on day of pickup plus single dose of decapeptyl 0.1 mg on day of embryo transfer Receives: Drug: Progesterone IM of 100 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
cycle pregnancy rate
pregnancy rate per started cycle
Measured: 6 weeks
Secondary outcomes (1)
implantation rate, multiple pregnancy rate, ongoing pregnancy rate ,live birth rate
implantation rate,multible pregnancy rate, abortion rate
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2013 (estimated)
- Study startMar 2013
- Primary completionDec 2014
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for IVFStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 220 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mansoura Integrated Fertility Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Emad Mohamad Sedeek, Mansoura Integrated Fertility Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01790282
- Sponsor's protocol ID
- E2 luteal support in ICSI
- Status last verified
- Jun 2022
- First submitted
- 8 Feb 2013
- Last updated
- 21 Jun 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Gelbaya TA, Kyrgiou M, Tsoumpou I, Nardo LG. The use of estradiol for luteal phase support in in vitro fertilization/intracytoplasmic sperm injection cycles: a systematic review and meta-analysis. Fertil Steril. 2008 Dec;90(6):2116-25. doi: 10.1016/j.fertnstert.2007.10.053. Epub 2008 Jan 7.
PubMed 18178194Sunkara SK, Rittenberg V, Raine-Fenning N, Bhattacharya S, Zamora J, Coomarasamy A. Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. Hum Reprod. 2011 Jul;26(7):1768-74. doi: 10.1093/humrep/der106. Epub 2011 May 10.
PubMed 21558332
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Is E2 Luteal Support in High Responder Long Gn-RH Agonist ICSI Cycles Detrimental to Cycle Outcome ? A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT01790282
- Acronym / sponsor ID
- E2 luteal support in ICSI
- Conditions
- IVF, Infertility
- Keywords
- luteal support, high responder, ICSI, cycle outcome
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 220 participants (actual)
- Lead sponsor
- Mansoura Integrated Fertility CenterUniversity, hospital or other
- Study start
- Mar 2013
- Primary completion
- Dec 2014 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 13 Feb 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study if supporting luteal phase of high responder (high egg production or high Estradiol level) long Gn_Rh agonist protocol ICSI/IVF cycle by combined Estradiol and progesterone impairs or improves outcome in terms of pregnancy and implanation rates.
Detailed description
The role of estradiol (E2) luteal support is still debated after more than a decade of use. Two recent met analyses (Gelbaya et al 2008) \&(Jee et al 2010)( ) has shown that the addition of E2 to P4 for luteal phase support in IVF/ICSI cycles has no beneficial effect on pregnancy rates. However they commented that the data in the literature are, limited and heterogeneous, precluding the extraction of clear and definite conclusions. Previous met analysis ( Pritts and Atwood 2002 ) and an update (Fatemi et al 2007 ) and subsequent randomized trials ( Ghanem et al 2009 , Var et al 2011 ) reported beneficial effects of adding E2 to luteal P4 support. Recent retrospective studies have shown that high response in terms of excess egg production ( >15 . ) and or high E2 (Chen et al 2007,Kyrou et al 2009, Sunkara 2011 ) are detrimental to cycle outcome. This prospective randomized trial aims to study whether adding E2 to P4 luteal support in high ovarian responders is detrimental to cycle outcome or not
--------------- Gelbaya TA, KyrgiouM, Tsoumpou I, Nardo LG. The use of estradiol for luteal phase support in in vitro fertilization/intracytoplasmic sperminjec- tion cycles: a systematic review and meta-analysis. Fertil Steril 2008;90: 2116-25.
Jee BC, Suh CS, Kim SH, Kim YB, Moon SY. Effects of estradiol supplementation during the luteal phase of in vitro fertilization cycles: a meta-analysis Fertil Steril. 2010 Feb;93(2):428-36
Pritts EA, Atwood AK. Luteal phase support in infertility treatment: a meta-analysis of randomized trials. Hum Reprod 2002;17:2287-99 Fatemi HM, Popovic-Todorovic B, Papanikolaou E, Donoso P,Devroey P. An update of luteal phase support in stimulated IVF cycles.Hum Reprod Update 2007;13:581.
- Ghanem M E., Ehab E. Sadek, Elboghdady L. A.. Helal A S, Gamal Anas, Eldiasty A Bakre N I., Houssen M .The effect of luteal phase support protocol on cycle outcome and luteal phase hormone profile in long agonist protocol intracytoplasmic sperm injection cycles: a randomized clinical trial , Fertility and Sterility 2009 92: 486-493
Var T, Tonguc EA, Doğanay M, Gulerman C, Gungor T, Mollamahmutoglu L. A comparison of the effects of three different luteal phase support protocols on in vitro fertilization outcomes: a randomized clinical trial. Fertil Steril. 2011 Mar 1;95(3):985-9.
van der Gaast, Eijkemans JB, de Boer EJ, Burger CW , van Leeuwen FE, Fauser BCJM , and Macklon NS Optimum number of oocytes for a successful first IVF treatment cycle Reproductive BioMedicine Online 2006 ; 13: 476-480
Sunkara SK, Rittenberg V, Raine-Fenning N, Bhattacharya S, Zamora J, Coomarasamy A. Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. Hum Reprod 2011; 26: 1768-1774
Chen QJ, Sun XX, Li L, Gao XH, Wu Y, Gemzell-Danielsson K, Cheng LN Effects of ovarian high response on implantation and pregnancy outcome during controlled ovarian hyperstimulation (with GnRH agonist and rFSH). Acta Obstet Gynecol Scand. 2007;86:849-54 Kyrou D., Popovic-Todorovic B., Fatemi H.M1, Bourgain C, Haentjens P., Van Landuyt L., and. Devroey P Does the estradiol level on the day of human chorionic gonadotrophin administration have an impact on pregnancy rates in patients treated with rec-FSH/GnRH antagonist? Hum Reprod 2009, 2902-2909,
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| estradiole - progesterone arm | Experimental | Drug: estradiol plus progesterone 100 mg IM injection, Drug: Progesterone IM of 100 mgCases are given estradiole valerate 2mg 3 times /day from day of ovum pick up until the time of pregnancy test two weeks together with daily IM injection of 100 progesterone starting . Single intramuscular 0.1 mg decapeptyl are given on day of transfer |
| Progesterone only arm | Active comparator | Drug: Progesterone IM of 100 mgPatient are given 100 mg progesterone daily starting on day of pickup plus single dose of decapeptyl 0.1 mg on day of embryo transfer |
Who may qualify
- Ages
- 18 to 39 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- age<40 years,
- first ICSI cycle,
- third day FSH< 10 mIU/mL,
- serum E2 level on day of hCG administration <4,000 pg/mL,
- number of ova obtained >15
Key exclusion criteria (5 listed)
- age 40 years or more,
- basal FSH 10 mIU/mL or more ,
- eggs retrieved 15 or less ,
- E2 level on day of hCG administration 4000 or more pg/ mL or more,
- repeat ICSI , need for PGD, presence of myoma , hydrosalpinx (unless disconnected)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| estradiol plus progesterone 100 mg IM injectionAlso: estradiole valerate 2mg,, Prontogest 100 mgestradile valaerate 2mg plus progesterone 100 mg/day support arm :E2 valerate 2mg three times /day are given to the arm cases plus P4 100 IM/day for 14 days starting on day of ovum pickup and single IM injection of 0.1 mg decapeptyl on day of ET | Drug | estradiole - progesterone arm |
| Progesterone IM of 100 mgAlso: prontogest 100 mg ampolesStarting on day of ovum pickup ICSI cases are given prontogest 100 mg IM /day plus single dose dose of treptorline 0.1mg is given sc on day of embryo transfer | Drug | Progesterone only arm, estradiole - progesterone arm |
Primary outcome
cycle pregnancy rate
Time frame: 6 weeks
pregnancy rate per started cycle
1 secondary outcome
implantation rate, multiple pregnancy rate, ongoing pregnancy rate ,live birth rate
Time frame: 6 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2022.
- Background: PubMed 18178194Gelbaya TA, Kyrgiou M, Tsoumpou I, Nardo LG. The use of estradiol for luteal phase support in in vitro fertilization/intracytoplasmic sperm injection cycles: a systematic review and meta-analysis. Fertil Steril. 2008 Dec;90(6):2116-25. doi: 10.1016/j.fertnstert.2007.10.053. Epub 2008 Jan 7.
- Background: PubMed 21558332Sunkara SK, Rittenberg V, Raine-Fenning N, Bhattacharya S, Zamora J, Coomarasamy A. Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. Hum Reprod. 2011 Jul;26(7):1768-74. doi: 10.1093/humrep/der106. Epub 2011 May 10.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing estradiol plus progesterone 100 mg IM injection and Progesterone IM of 100 mg in people with IVF and Infertility, run by Mansoura Integrated Fertility Center at 1 site in Egypt.
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 5 inclusion and 5 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 21 Jun 2022. 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 Egypt. 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?
cycle pregnancy rate (time frame: 6 weeks). 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 NCT01790282, which also lists 2 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 21 Jun 2022.