InfertilityNCT01367912
Timing of Estrogen Support During the Luteal Phase of in Vitro Fertilization (IVF)/Intracytoplasmic Sperm Injection (ICSI) Cycle
A study testing estradiol tablet in people with Infertility, run by Zekai Tahir Burak Women's Health Research and Education Hospital at 1 site in Turkey (Türkiye).
Trial summary
To test the hypothesis that adding estradiol (E2) to progesterone supplementation later in the luteal phase of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles, rather than earlier in the luteal phase, improves clinical pregnancy rates (PRs). Read more about this study
- Who is it for?
- Ages Up to 40 years, women only
- Conditions the study is for
- Infertility
- What is being tested?
- estradiol tablet
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 301 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- Feb 2008to Nov 2008
- 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 Up to 40 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- All patients on long GnRH agonist protocol with controlled ovarian hyperstimulation who were seen in our IVF clinic between February and November 2008, and who have E2 levels on the day of hCG administration >2500 pg/dl
Who cannot join
- Presence of azoospermia requiring testicular sperm extraction procedure
- endometriosis greater than stage II
- unilateral oophorectomy, polycystic ovarian syndrome (PCOS)
- secondary infertility
- age greater than 40 yrs and a basal follicle stimulating hormone (FSH) level higher than 12 mIU/ml were exclusion criteria
Trial locations and contacts
1 site in 1 country.
Turkey (Türkiye)1 site
Zekai Tahir Burak Maternity and Teaching Hospital
Ankara, 06220
About this study
Official title: Timing of Estrogen Support During the Luteal Phase of IVF / Intracytoplasmic Sperm Injection Cycle: a Randomized Controlled Trial
To test the hypothesis that adding estradiol (E2) to progesterone supplementation later in the luteal phase of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles, rather than earlier in the luteal phase, improves clinical pregnancy rates (PRs).
Read the detailed description
Several studies reported that elevated E2 may have a detrimental effect on endometrial receptivity and embryo. This conflict was the starting point of our study. The investigators thought that this luteal decrease in E2 level could be prevented by adding estradiol just before the receptivity window is open, instead of adding earlier in the luteal phase which could result in defective embryo implantation.
- Conditions
- Infertility
- Being tested
- estradiol tablet
- Keywords
- Luteal phase support, estradiol supplementation, IVF/ICSI, clinical pregnancy rate
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
estradiol tabletDrug
Also called estrofem 2 mg tablet, Novo Nordisk, Bagsvaerd, Denmark
received 2 mg estradiol tablets orally two times daily beginning from the first day after hCG injection, in addition to vaginal progesterone gel
estradiol tabletDrug
Also called estrofem 2 mg tablet, Novo Nordisk, Bagsvaerd, Denmark
received 2 mg estradiol tablets orally two times daily beginning from the fifth day after hCG injection, in addition to vaginal progesterone gel.
| Study group | Role | What they receive |
|---|---|---|
| Progesterone only group | No intervention | received a single daily application of vaginal progesterone gel beginning from the day of OPU and continued at least until pregnancy was ruled out by a negative serum ß-hCG measurement performed on the 14th day after embryo transfer with no E2 added |
| Progesterone+Early Estradiol group | Active comparator | received 2 mg estradiol tablets orally two times daily beginning from the first day after hCG injection, in addition to vaginal progesterone gel Receives: Drug: estradiol tablet |
| Progesterone+Late estradiol group | Active comparator | received 2 mg estradiol tablets orally two times daily beginning from the fifth day after hCG injection, in addition to vaginal progesterone gel Receives: Drug: estradiol tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical pregnancy rate
Clinical pregnancies were detected with the confirmation of positive fetal cardiac activities by transvaginal sonography in the sixth gestational week.
Measured: sixth gestational week.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2011 (estimated)
- Study startFeb 2008
- Primary completionNov 2008
- Study completionNov 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (30)Papers the sponsor has linked to this study.
- Other trials for InfertilityStudies 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
- Single blind
- Who is masked
- Investigator
- Enrolment
- 301 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zekai Tahir Burak Women's Health Research and Education Hospital
- Sponsor type
- University, hospital or other
- Investigators
- Leyla Mollamahmutoğlu, MD, Study director, Zekai Tahir Burak Women's Health Research and Education Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01367912
- Sponsor's protocol ID
- ZTB
- Status last verified
- Nov 2008
- First submitted
- 3 Jun 2011
- Last updated
- 7 Jun 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
Ubaldi F, Bourgain C, Tournaye H, Smitz J, Van Steirteghem A, Devroey P. Endometrial evaluation by aspiration biopsy on the day of oocyte retrieval in the embryo transfer cycles in patients with serum progesterone rise during the follicular phase. Fertil Steril. 1997 Mar;67(3):521-6. doi: 10.1016/s0015-0282(97)80080-5.
PubMed 9091341Kolibianakis EM, Devroey P. The luteal phase after ovarian stimulation. Reprod Biomed Online. 2002;5 Suppl 1:26-35. doi: 10.1016/s1472-6483(11)60214-9.
PubMed 12537779Fauser BC, Devroey P. Reproductive biology and IVF: ovarian stimulation and luteal phase consequences. Trends Endocrinol Metab. 2003 Jul;14(5):236-42. doi: 10.1016/s1043-2760(03)00075-4.
PubMed 12826330Devreker F, Govaerts I, Bertrand E, Van den Bergh M, Gervy C, Englert Y. The long-acting gonadotropin-releasing hormone analogues impaired the implantation rate. Fertil Steril. 1996 Jan;65(1):122-6.
PubMed 8557126Daya S, Gunby J. Luteal phase support in assisted reproduction cycles. Cochrane Database Syst Rev. 2004;(3):CD004830. doi: 10.1002/14651858.CD004830.
PubMed 15266541Pritts EA, Atwood AK. Luteal phase support in infertility treatment: a meta-analysis of the randomized trials. Hum Reprod. 2002 Sep;17(9):2287-99. doi: 10.1093/humrep/17.9.2287.
PubMed 12202415Jee 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. doi: 10.1016/j.fertnstert.2009.02.033. Epub 2009 Apr 1.
PubMed 19342034Gelbaya 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 18178194Kolibianakis EM, Venetis CA, Papanikolaou EG, Diedrich K, Tarlatzis BC, Griesinger G. Estrogen addition to progesterone for luteal phase support in cycles stimulated with GnRH analogues and gonadotrophins for IVF: a systematic review and meta-analysis. Hum Reprod. 2008 Jun;23(6):1346-54. doi: 10.1093/humrep/den115. Epub 2008 Apr 11.
PubMed 18408017Buvat J, Marcolin G, Guittard C, Dehaene JL, Herbaut JC, Louvet AL. [Luteal support after administration of an LHRH analog for in vitro fertilization. Superiority of vaginal progesterone in comparison with oral progesterone]. Presse Med. 1990 Mar 24;19(11):527. No abstract available. French.
PubMed 2138757Farhi J, Weissman A, Steinfeld Z, Shorer M, Nahum H, Levran D. Estradiol supplementation during the luteal phase may improve the pregnancy rate in patients undergoing in vitro fertilization-embryo transfer cycles. Fertil Steril. 2000 Apr;73(4):761-6. doi: 10.1016/s0015-0282(99)00632-9.
PubMed 10731538Bergh PA, Navot D. The impact of embryonic development and endometrial maturity on the timing of implantation. Fertil Steril. 1992 Sep;58(3):537-42. doi: 10.1016/s0015-0282(16)55259-5.
PubMed 1521649Muasher S, Acosta AA, Garcia JE, Jones GS, Jones HW Jr. Luteal phase serum estradiol and progesterone in in vitro fertilization. Fertil Steril. 1984 Jun;41(6):838-43. doi: 10.1016/s0015-0282(16)47895-7.
PubMed 6427017Yang JH, Chen HF, Lien YR, Chen SU, Ho HN, Yang YS. Elevated E2: oocyte ratio in women undergoing IVF and tubal ET. Correlation with a decrease in the implantation rate. J Reprod Med. 2001 May;46(5):434-8.
PubMed 11396368Valbuena D, Martin J, de Pablo JL, Remohi J, Pellicer A, Simon C. Increasing levels of estradiol are deleterious to embryonic implantation because they directly affect the embryo. Fertil Steril. 2001 Nov;76(5):962-8. doi: 10.1016/s0015-0282(01)02018-0.
PubMed 11704118
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Timing of Estrogen Support During the Luteal Phase of IVF / Intracytoplasmic Sperm Injection Cycle: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT01367912
- Acronym / sponsor ID
- ZTB
- Conditions
- Infertility
- Keywords
- Luteal phase support, estradiol supplementation, IVF/ICSI, clinical pregnancy rate
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 301 participants (actual)
- Lead sponsor
- Zekai Tahir Burak Women's Health Research and Education HospitalUniversity, hospital or other
- Study start
- Feb 2008
- Primary completion
- Nov 2008 (actual)
- Study completion
- Nov 2008 (actual)
- First posted
- 7 Jun 2011 (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.
To test the hypothesis that adding estradiol (E2) to progesterone supplementation later in the luteal phase of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles, rather than earlier in the luteal phase, improves clinical pregnancy rates (PRs).
Detailed description
Several studies reported that elevated E2 may have a detrimental effect on endometrial receptivity and embryo. This conflict was the starting point of our study. The investigators thought that this luteal decrease in E2 level could be prevented by adding estradiol just before the receptivity window is open, instead of adding earlier in the luteal phase which could result in defective embryo implantation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Progesterone only group | No intervention | –received a single daily application of vaginal progesterone gel beginning from the day of OPU and continued at least until pregnancy was ruled out by a negative serum ß-hCG measurement performed on the 14th day after embryo transfer with no E2 added |
| Progesterone+Early Estradiol group | Active comparator | Drug: estradiol tabletreceived 2 mg estradiol tablets orally two times daily beginning from the first day after hCG injection, in addition to vaginal progesterone gel |
| Progesterone+Late estradiol group | Active comparator | Drug: estradiol tabletreceived 2 mg estradiol tablets orally two times daily beginning from the fifth day after hCG injection, in addition to vaginal progesterone gel |
Who may qualify
- Ages
- Up to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (1 listed)
- All patients on long GnRH agonist protocol with controlled ovarian hyperstimulation who were seen in our IVF clinic between February and November 2008, and who have E2 levels on the day of hCG administration >2500 pg/dl
Key exclusion criteria (5 listed)
- Presence of azoospermia requiring testicular sperm extraction procedure
- endometriosis greater than stage II
- unilateral oophorectomy, polycystic ovarian syndrome (PCOS)
- secondary infertility
- age greater than 40 yrs and a basal follicle stimulating hormone (FSH) level higher than 12 mIU/ml were exclusion criteria
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 tabletAlso: estrofem 2 mg tablet, Novo Nordisk, Bagsvaerd, Denmarkreceived 2 mg estradiol tablets orally two times daily beginning from the first day after hCG injection, in addition to vaginal progesterone gel | Drug | Progesterone+Early Estradiol group |
| estradiol tabletAlso: estrofem 2 mg tablet, Novo Nordisk, Bagsvaerd, Denmarkreceived 2 mg estradiol tablets orally two times daily beginning from the fifth day after hCG injection, in addition to vaginal progesterone gel. | Drug | Progesterone+Late estradiol group |
Primary outcome
Clinical pregnancy rate
Time frame: sixth gestational week.
Clinical pregnancies were detected with the confirmation of positive fetal cardiac activities by transvaginal sonography in the sixth gestational week.
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 7 Jun 2011.
- Background: PubMed 9091341Ubaldi F, Bourgain C, Tournaye H, Smitz J, Van Steirteghem A, Devroey P. Endometrial evaluation by aspiration biopsy on the day of oocyte retrieval in the embryo transfer cycles in patients with serum progesterone rise during the follicular phase. Fertil Steril. 1997 Mar;67(3):521-6. doi: 10.1016/s0015-0282(97)80080-5.
- Background: PubMed 12537779Kolibianakis EM, Devroey P. The luteal phase after ovarian stimulation. Reprod Biomed Online. 2002;5 Suppl 1:26-35. doi: 10.1016/s1472-6483(11)60214-9.
- Background: PubMed 12826330Fauser BC, Devroey P. Reproductive biology and IVF: ovarian stimulation and luteal phase consequences. Trends Endocrinol Metab. 2003 Jul;14(5):236-42. doi: 10.1016/s1043-2760(03)00075-4.
- Background: PubMed 8557126Devreker F, Govaerts I, Bertrand E, Van den Bergh M, Gervy C, Englert Y. The long-acting gonadotropin-releasing hormone analogues impaired the implantation rate. Fertil Steril. 1996 Jan;65(1):122-6.
- Background: PubMed 15266541Daya S, Gunby J. Luteal phase support in assisted reproduction cycles. Cochrane Database Syst Rev. 2004;(3):CD004830. doi: 10.1002/14651858.CD004830.
- Background: PubMed 12202415Pritts EA, Atwood AK. Luteal phase support in infertility treatment: a meta-analysis of the randomized trials. Hum Reprod. 2002 Sep;17(9):2287-99. doi: 10.1093/humrep/17.9.2287.
- Background: PubMed 19342034Jee 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. doi: 10.1016/j.fertnstert.2009.02.033. Epub 2009 Apr 1.
- 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 18408017Kolibianakis EM, Venetis CA, Papanikolaou EG, Diedrich K, Tarlatzis BC, Griesinger G. Estrogen addition to progesterone for luteal phase support in cycles stimulated with GnRH analogues and gonadotrophins for IVF: a systematic review and meta-analysis. Hum Reprod. 2008 Jun;23(6):1346-54. doi: 10.1093/humrep/den115. Epub 2008 Apr 11.
- Background: PubMed 2138757Buvat J, Marcolin G, Guittard C, Dehaene JL, Herbaut JC, Louvet AL. [Luteal support after administration of an LHRH analog for in vitro fertilization. Superiority of vaginal progesterone in comparison with oral progesterone]. Presse Med. 1990 Mar 24;19(11):527. No abstract available. French.
- Background: PubMed 10731538Farhi J, Weissman A, Steinfeld Z, Shorer M, Nahum H, Levran D. Estradiol supplementation during the luteal phase may improve the pregnancy rate in patients undergoing in vitro fertilization-embryo transfer cycles. Fertil Steril. 2000 Apr;73(4):761-6. doi: 10.1016/s0015-0282(99)00632-9.
- Background: PubMed 1521649Bergh PA, Navot D. The impact of embryonic development and endometrial maturity on the timing of implantation. Fertil Steril. 1992 Sep;58(3):537-42. doi: 10.1016/s0015-0282(16)55259-5.
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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.
Leyla Mollamahmutoğlu, MD study director
Zekai Tahir Burak Women's Health Research and Education Hospital
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 tablet in people with Infertility, run by Zekai Tahir Burak Women's Health Research and Education Hospital 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 1 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 7 Jun 2011. 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?
Clinical pregnancy rate (time frame: sixth gestational week.). 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 NCT01367912, which also lists 30 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 7 Jun 2011.