Ovarian Hyperstimulation SyndromeNCT05362734
Freeze All Strategy Versus Fresh Embryo Transfer After GnRH Analogue Trigger
An observational study of Ovarian Hyperstimulation Syndrome and Pregnancy Related, run by Istituto Clinico Humanitas.
Trial summary
Ovarian hyperstimulation syndrome (OHSS) is one of the most dangerous complications of assisted reproduction technology (ART), described in approximatively 3 to 10% of stimulation cycles although an underestimation of the real incidence has been suggested. Read more about this study
- Who is it for?
- Ages 20 to 45 years, women only
- Conditions the study is for
- Ovarian Hyperstimulation Syndrome, Pregnancy Related
- What is being tested?
- obstetric outcomes after fresh versus cryopreserved embryo transfer
- Type of treatment
- Lifestyle or therapy programme
- How many people
- 1,396 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2012to 31 Dec 2020
- 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 20 to 45 years
- Women only
- No healthy volunteers
- Adult
Study population: The study database includes all Oocyte Retrievals (OR) performed between 01/01/2012 and 31/12/2020 at Humanitas Fertility Center after antagonist protocol stimulation and trigger with GnRH agonist.
Who may be able to join
- patients undergoing ART cycle with antagonist protocol stimulation and trigger with GnRH agonist
- patients are believed at risk of OHSS at time of trigger based on size and number of follicles developed (≥18 follicles with diameter 12 mm at induction).
Who cannot join
- hypogonadotropic hypogonadism
- other ART protocols
- any patient that underwent freeze-all strategy in order to perform pre-implantation genetic testing (PGT)
- oncological or deferring motherhood freezing procedures
About this study
Ovarian hyperstimulation syndrome (OHSS) is one of the most dangerous complications of assisted reproduction technology (ART), described in approximatively 3 to 10% of stimulation cycles although an underestimation of the real incidence has been suggested.
The use in clinical practice of GnRH antagonist has made it possible to perform the trigger with GnRH analogues, with the advantage of considerably reducing the risk of OHSS.
Read the detailed description
The main concerns about the trigger with analogue are about obstetric outcomes, since it may increase the Abortion Rate (AR) and reduce the Ongoing Pregnancy Rate (OPR) due to luteal phase deficiency, and on the other hand about oocyte quality and competence.
While in order to maximize the chance of pregnancy at fresh embryo transfer after GnRHa trigger, several studies have focused on the importance of luteal phase support, other authors suggest that the best strategy is freeze-all: cryopreservation of all the obtained embryos and subsequent single embryo transfers.
However, data about oocyte quality, retrieval rate, pregnancy rate and reduced occurrence of complications such as OHSS, especially on the very first embryo transfer, are still scarce.
- Being tested
- obstetric outcomes after fresh versus cryopreserved embryo transfer
- Medical subject headings
- Ovarian Hyperstimulation Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
obstetric outcomes after fresh versus cryopreserved embryo transferBehavioural
measure of ongoing pregnancy rate, delivery rate, abortion rate, ectopic pregnancy rate, multiple birth rate, ovarian hyperstimulation syndrome incidence, drop out rate
| Study group | Role | What they receive |
|---|---|---|
| First fresh embryo transfer (group A) | The two groups analysed were defined according to the modality of first embryo transfer: cycles in which a fresh ET was performed at first, after a dual triggering or a rescue protocol (Group A) and cycles where a frozen-thawed ET was performed at first, after being chosen a freeze-all strategy (Group B). Receives: Behavioral: obstetric outcomes after fresh versus cryopreserved embryo transfer | |
| First cryopreserved embryo transfer (group B) | The two groups analysed were defined according to the modality of first embryo transfer: cycles in which a fresh ET was performed at first, after a dual triggering or a rescue protocol (Group A) and cycles where a frozen-thawed ET was performed at first, after being chosen a freeze-all strategy (Group B). Receives: Behavioral: obstetric outcomes after fresh versus cryopreserved embryo transfer |
What is being measured
The primary outcome is the main question the study is designed to answer.
ongoing pregnancy rate
number of viable pregnancies that had completed at least 12 weeks of gestation on the total number of ETs performed
Measured: 8 years
delivery rate
number of deliveries of one or more live births over the total performed ET
Measured: 8 years
Secondary outcomes (3)
Other pregnancy outcomes
ectopic pregnancy rate, miscarriage rate, multiple Birth Rate
Measured: 8 years
Safety profile
Severe ovarian hyperstimulation syndrome incidence
Measured: 8 years
the dropout rate
number of cycles in which any live birth (from either ART and/or spontaneous conceive) was not achieved and still some embryos or oocytes had to be thawed
Measured: 8 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2022
- Study start1 Jan 2012
- Primary completion31 Dec 2020
- Study completion31 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Ovarian Hyperstimulation SyndromeStudies of the same condition, open and under way.
- More trials run by Istituto Clinico HumanitasThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 1,396 participants (actual)
Sponsor and investigators
- Lead sponsor
- Istituto Clinico Humanitas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05362734
- Sponsor's protocol ID
- 999
- Status last verified
- Jul 2023
- First submitted
- 2 May 2022
- Last updated
- 7 Jul 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kupka MS, Ferraretti AP, de Mouzon J, Erb K, D'Hooghe T, Castilla JA, Calhaz-Jorge C, De Geyter C, Goossens V; European IVF-Monitoring Consortium, for the European Society of Human Reproduction and Embryology. Assisted reproductive technology in Europe, 2010: results generated from European registers by ESHREdagger. Hum Reprod. 2014 Oct 10;29(10):2099-113. doi: 10.1093/humrep/deu175. Epub 2014 Jul 27.
PubMed 25069504Humaidan P, Nelson SM, Devroey P, Coddington CC, Schwartz LB, Gordon K, Frattarelli JL, Tarlatzis BC, Fatemi HM, Lutjen P, Stegmann BJ. Ovarian hyperstimulation syndrome: review and new classification criteria for reporting in clinical trials. Hum Reprod. 2016 Sep;31(9):1997-2004. doi: 10.1093/humrep/dew149. Epub 2016 Jun 23.
PubMed 27343272Levi-Setti PE, Di Segni N, Gargasole C, Ronchetti C, Cirillo F. Ovarian Hyperstimulation: Diagnosis, Prevention, and Management. Semin Reprod Med. 2021 Nov;39(5-06):170-179. doi: 10.1055/s-0041-1736492. Epub 2021 Oct 13.
PubMed 34644798De Geyter C, Calhaz-Jorge C, Kupka MS, Wyns C, Mocanu E, Motrenko T, Scaravelli G, Smeenk J, Vidakovic S, Goossens V; European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). ART in Europe, 2015: results generated from European registries by ESHRE. Hum Reprod Open. 2020 Feb 24;2020(1):hoz038. doi: 10.1093/hropen/hoz038. eCollection 2020.
PubMed 32123753Humaidan P, Kol S, Papanikolaou EG; Copenhagen GnRH Agonist Triggering Workshop Group. GnRH agonist for triggering of final oocyte maturation: time for a change of practice? Hum Reprod Update. 2011 Jul-Aug;17(4):510-24. doi: 10.1093/humupd/dmr008. Epub 2011 Mar 30.
PubMed 21450755Humaidan P, Bredkjaer HE, Bungum L, Bungum M, Grondahl ML, Westergaard L, Andersen CY. GnRH agonist (buserelin) or hCG for ovulation induction in GnRH antagonist IVF/ICSI cycles: a prospective randomized study. Hum Reprod. 2005 May;20(5):1213-20. doi: 10.1093/humrep/deh765. Epub 2005 Mar 10.
PubMed 15760966Lawrenz B, Coughlan C, Fatemi HM. Individualized luteal phase support. Curr Opin Obstet Gynecol. 2019 Jun;31(3):177-182. doi: 10.1097/GCO.0000000000000530.
PubMed 30855289Abbara A, Islam R, Clarke SA, Jeffers L, Christopoulos G, Comninos AN, Salim R, Lavery SA, Vuong TNL, Humaidan P, Kelsey TW, Trew GH, Dhillo WS. Clinical parameters of ovarian hyperstimulation syndrome following different hormonal triggers of oocyte maturation in IVF treatment. Clin Endocrinol (Oxf). 2018 Jun;88(6):920-927. doi: 10.1111/cen.13569. Epub 2018 Mar 6.
PubMed 29446481Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, Rienzi L, Sunde A, Schmidt L, Cooke ID, Simpson JL, van der Poel S. The International Glossary on Infertility and Fertility Care, 2017. Fertil Steril. 2017 Sep;108(3):393-406. doi: 10.1016/j.fertnstert.2017.06.005. Epub 2017 Jul 29.
PubMed 28760517ESHRE Special Interest Group of Embryology and Alpha Scientists in Reproductive Medicine. Electronic address: coticchio.biogenesi@grupposandonato.it. The Vienna consensus: report of an expert meeting on the development of ART laboratory performance indicators. Reprod Biomed Online. 2017 Nov;35(5):494-510. doi: 10.1016/j.rbmo.2017.06.015. Epub 2017 Aug 4.
PubMed 28784335ESHRE Clinic PI Working Group; Vlaisavljevic V, Apter S, Capalbo A, D'Angelo A, Gianaroli L, Griesinger G, Kolibianakis EM, Lainas G, Mardesic T, Motrenko T, Pelkonen S, Romualdi D, Vermeulen N, Tilleman K. The Maribor consensus: report of an expert meeting on the development of performance indicators for clinical practice in ART. Hum Reprod Open. 2021 Jul 3;2021(3):hoab022. doi: 10.1093/hropen/hoab022. eCollection 2021.
PubMed 34250273Tomas C, Alsbjerg B, Martikainen H, Humaidan P. Pregnancy loss after frozen-embryo transfer--a comparison of three protocols. Fertil Steril. 2012 Nov;98(5):1165-9. doi: 10.1016/j.fertnstert.2012.07.1058. Epub 2012 Jul 27.
PubMed 22840239ESHRE working group on Ectopic Pregnancy; Kirk E, Ankum P, Jakab A, Le Clef N, Ludwin A, Small R, Tellum T, Toyli M, Van den Bosch T, Jurkovic D. Terminology for describing normally sited and ectopic pregnancies on ultrasound: ESHRE recommendations for good practice. Hum Reprod Open. 2020 Dec 16;2020(4):hoaa055. doi: 10.1093/hropen/hoaa055. eCollection 2020.
PubMed 33354626Committee on Practice Bulletins-Gynecology. ACOG Practice Bulletin No. 191: Tubal Ectopic Pregnancy. Obstet Gynecol. 2018 Feb;131(2):e65-e77. doi: 10.1097/AOG.0000000000002464.
PubMed 29232273Sunkara SK, Zheng W, D'Hooghe T, Longobardi S, Boivin J. Time as an outcome measure in fertility-related clinical studies: long-awaited. Hum Reprod. 2020 Aug 1;35(8):1732-1739. doi: 10.1093/humrep/deaa138.
PubMed 32644107
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Freeze All Strategy Versus Fresh Embryo Transfer After GnRH Analogue Trigger
- ClinicalTrials.gov ID
- NCT05362734
- Acronym / sponsor ID
- 999
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,396 participants (actual)
- Lead sponsor
- Istituto Clinico HumanitasUniversity, hospital or other
- Study start
- 1 Jan 2012 (actual)
- Primary completion
- 31 Dec 2020 (actual)
- Study completion
- 31 Dec 2020 (actual)
- First posted
- 5 May 2022 (actual)
- 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.
Ovarian hyperstimulation syndrome (OHSS) is one of the most dangerous complications of assisted reproduction technology (ART), described in approximatively 3 to 10% of stimulation cycles although an underestimation of the real incidence has been suggested.
The use in clinical practice of GnRH antagonist has made it possible to perform the trigger with GnRH analogues, with the advantage of considerably reducing the risk of OHSS.
Detailed description
The main concerns about the trigger with analogue are about obstetric outcomes, since it may increase the Abortion Rate (AR) and reduce the Ongoing Pregnancy Rate (OPR) due to luteal phase deficiency, and on the other hand about oocyte quality and competence.
While in order to maximize the chance of pregnancy at fresh embryo transfer after GnRHa trigger, several studies have focused on the importance of luteal phase support, other authors suggest that the best strategy is freeze-all: cryopreservation of all the obtained embryos and subsequent single embryo transfers.
However, data about oocyte quality, retrieval rate, pregnancy rate and reduced occurrence of complications such as OHSS, especially on the very first embryo transfer, are still scarce.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| First fresh embryo transfer (group A) | – | Behavioral: obstetric outcomes after fresh versus cryopreserved embryo transferThe two groups analysed were defined according to the modality of first embryo transfer: cycles in which a fresh ET was performed at first, after a dual triggering or a rescue protocol (Group A) and cycles where a frozen-thawed ET was performed at first, after being chosen a freeze-all strategy (Group B). |
| First cryopreserved embryo transfer (group B) | – | Behavioral: obstetric outcomes after fresh versus cryopreserved embryo transferThe two groups analysed were defined according to the modality of first embryo transfer: cycles in which a fresh ET was performed at first, after a dual triggering or a rescue protocol (Group A) and cycles where a frozen-thawed ET was performed at first, after being chosen a freeze-all strategy (Group B). |
Who may qualify
- Ages
- 20 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- The study database includes all Oocyte Retrievals (OR) performed between 01/01/2012 and 31/12/2020 at Humanitas Fertility Center after antagonist protocol stimulation and trigger with GnRH agonist.
Key inclusion criteria (2 listed)
- patients undergoing ART cycle with antagonist protocol stimulation and trigger with GnRH agonist
- patients are believed at risk of OHSS at time of trigger based on size and number of follicles developed (≥18 follicles with diameter 12 mm at induction).
Key exclusion criteria (4 listed)
- hypogonadotropic hypogonadism
- other ART protocols
- any patient that underwent freeze-all strategy in order to perform pre-implantation genetic testing (PGT)
- oncological or deferring motherhood freezing procedures
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 |
|---|---|---|
| obstetric outcomes after fresh versus cryopreserved embryo transfermeasure of ongoing pregnancy rate, delivery rate, abortion rate, ectopic pregnancy rate, multiple birth rate, ovarian hyperstimulation syndrome incidence, drop out rate | Behavioural | First cryopreserved embryo transfer (group B), First fresh embryo transfer (group A) |
Primary outcome
ongoing pregnancy rate
Time frame: 8 years
number of viable pregnancies that had completed at least 12 weeks of gestation on the total number of ETs performed
delivery rate
Time frame: 8 years
number of deliveries of one or more live births over the total performed ET
3 secondary outcomes
Other pregnancy outcomes
Time frame: 8 years
Safety profile
Time frame: 8 years
the dropout rate
Time frame: 8 years
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 Jul 2023.
- Background: PubMed 25069504Kupka MS, Ferraretti AP, de Mouzon J, Erb K, D'Hooghe T, Castilla JA, Calhaz-Jorge C, De Geyter C, Goossens V; European IVF-Monitoring Consortium, for the European Society of Human Reproduction and Embryology. Assisted reproductive technology in Europe, 2010: results generated from European registers by ESHREdagger. Hum Reprod. 2014 Oct 10;29(10):2099-113. doi: 10.1093/humrep/deu175. Epub 2014 Jul 27.
- Background: PubMed 27343272Humaidan P, Nelson SM, Devroey P, Coddington CC, Schwartz LB, Gordon K, Frattarelli JL, Tarlatzis BC, Fatemi HM, Lutjen P, Stegmann BJ. Ovarian hyperstimulation syndrome: review and new classification criteria for reporting in clinical trials. Hum Reprod. 2016 Sep;31(9):1997-2004. doi: 10.1093/humrep/dew149. Epub 2016 Jun 23.
- Background: PubMed 34644798Levi-Setti PE, Di Segni N, Gargasole C, Ronchetti C, Cirillo F. Ovarian Hyperstimulation: Diagnosis, Prevention, and Management. Semin Reprod Med. 2021 Nov;39(5-06):170-179. doi: 10.1055/s-0041-1736492. Epub 2021 Oct 13.
- Background: PubMed 32123753De Geyter C, Calhaz-Jorge C, Kupka MS, Wyns C, Mocanu E, Motrenko T, Scaravelli G, Smeenk J, Vidakovic S, Goossens V; European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). ART in Europe, 2015: results generated from European registries by ESHRE. Hum Reprod Open. 2020 Feb 24;2020(1):hoz038. doi: 10.1093/hropen/hoz038. eCollection 2020.
- Background: PubMed 21450755Humaidan P, Kol S, Papanikolaou EG; Copenhagen GnRH Agonist Triggering Workshop Group. GnRH agonist for triggering of final oocyte maturation: time for a change of practice? Hum Reprod Update. 2011 Jul-Aug;17(4):510-24. doi: 10.1093/humupd/dmr008. Epub 2011 Mar 30.
- Background: PubMed 15760966Humaidan P, Bredkjaer HE, Bungum L, Bungum M, Grondahl ML, Westergaard L, Andersen CY. GnRH agonist (buserelin) or hCG for ovulation induction in GnRH antagonist IVF/ICSI cycles: a prospective randomized study. Hum Reprod. 2005 May;20(5):1213-20. doi: 10.1093/humrep/deh765. Epub 2005 Mar 10.
- Background: PubMed 30855289Lawrenz B, Coughlan C, Fatemi HM. Individualized luteal phase support. Curr Opin Obstet Gynecol. 2019 Jun;31(3):177-182. doi: 10.1097/GCO.0000000000000530.
- Background: PubMed 29446481Abbara A, Islam R, Clarke SA, Jeffers L, Christopoulos G, Comninos AN, Salim R, Lavery SA, Vuong TNL, Humaidan P, Kelsey TW, Trew GH, Dhillo WS. Clinical parameters of ovarian hyperstimulation syndrome following different hormonal triggers of oocyte maturation in IVF treatment. Clin Endocrinol (Oxf). 2018 Jun;88(6):920-927. doi: 10.1111/cen.13569. Epub 2018 Mar 6.
- Background: PubMed 28760517Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, Rienzi L, Sunde A, Schmidt L, Cooke ID, Simpson JL, van der Poel S. The International Glossary on Infertility and Fertility Care, 2017. Fertil Steril. 2017 Sep;108(3):393-406. doi: 10.1016/j.fertnstert.2017.06.005. Epub 2017 Jul 29.
- Background: PubMed 28784335ESHRE Special Interest Group of Embryology and Alpha Scientists in Reproductive Medicine. Electronic address: coticchio.biogenesi@grupposandonato.it. The Vienna consensus: report of an expert meeting on the development of ART laboratory performance indicators. Reprod Biomed Online. 2017 Nov;35(5):494-510. doi: 10.1016/j.rbmo.2017.06.015. Epub 2017 Aug 4.
- Background: PubMed 34250273ESHRE Clinic PI Working Group; Vlaisavljevic V, Apter S, Capalbo A, D'Angelo A, Gianaroli L, Griesinger G, Kolibianakis EM, Lainas G, Mardesic T, Motrenko T, Pelkonen S, Romualdi D, Vermeulen N, Tilleman K. The Maribor consensus: report of an expert meeting on the development of performance indicators for clinical practice in ART. Hum Reprod Open. 2021 Jul 3;2021(3):hoab022. doi: 10.1093/hropen/hoab022. eCollection 2021.
- Background: PubMed 22840239Tomas C, Alsbjerg B, Martikainen H, Humaidan P. Pregnancy loss after frozen-embryo transfer--a comparison of three protocols. Fertil Steril. 2012 Nov;98(5):1165-9. doi: 10.1016/j.fertnstert.2012.07.1058. Epub 2012 Jul 27.
- Individual participant dataSharing planned: No
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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.
Questions about this trial
What is this clinical trial studying?
An observational study of Ovarian Hyperstimulation Syndrome and Pregnancy Related, run by Istituto Clinico Humanitas.
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 2 inclusion and 4 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 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
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?
ongoing pregnancy rate (time frame: 8 years). The study lists 2 primary outcomes in all. 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 NCT05362734, which also lists 15 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 Jul 2023.