Ovarian Hyperstimulation SyndromePhase 4NCT01815138
Co-administration of Low Dose hCG at the Time of GnRH Agonist Trigger or 35 Hours Later for the Prevention of OHSS
A Phase 4 study testing hCG in people with Ovarian Hyperstimulation Syndrome, run by UConn Health at 1 site in United States.
Trial summary
This a prospective randomized double blind study involving patients at high risk of OHSS development with peak serum E2 levels < 4,000 pg/ml comparing the ongoing pregnancy rates in patients who receive adjuvant hCG 1,000 IU at the time of GnRH agonist trigger or adjuvant hCG 1,500 IU 35 hours after GnRH agonist… Read more about this study
- Who is it for?
- Ages 18 to 39 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Ovarian Hyperstimulation Syndrome
- What is being tested?
- hCG
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 89 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2013to Oct 2016
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Healthy volunteers accepted
- Adult
Who may be able to join
- Normal baseline serum follicle stimulating hormone, polycystic ovarian syndrome (PCOS), Polycystic ovarian morphology, Previous high responder or previous OHSS, must have > 14 follicles of over 11 mm in diameter and with peak serum E2 levels < 4,000 pg/mL on the day of trigger of oocyte maturation.
Who cannot join
- Hypothalamic dysfunction, Patients with < 14 follicles < 11 mm in diameter, peak serum E2 levels >= 4,000 pg/mL.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Connecticut Health Center
Farmington, Connecticut, 06030
About this study
Official title: A Prospective Double-blind Randomized Trial Comparing Pregnancy Rates After Low Dose Human Chorionic Gonadotropin (hCG) at the Time of Gonadotropin Releasing Hormone (GnRH) Agonist Trigger or 35 Hours Later for the Prevention of OHSS
This a prospective randomized double blind study involving patients at high risk of OHSS development with peak serum E2 levels < 4,000 pg/ml comparing the ongoing pregnancy rates in patients who receive adjuvant hCG 1,000 IU at the time of GnRH agonist trigger or adjuvant hCG 1,500 IU 35 hours after GnRH agonist trigger.
Read the detailed description
Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of controlled ovarian hyperstimulation which may result in significant morbidity and rarely mortality as well as significant financial and psychological distress. GnRH agonist trigger has been shown to be effective in OHSS prevention. However, the adoption of its use has not been widely accepted in view of concerns regarding potential impairment of implantation.
Intensive luteal phase supplementation with estrogen (E2) and progesterone (P) is important due to the strong evidence of abnormal luteal phase serum E2 and P profiles. However, it has been shown that optimal conception rates is not achieved for high risk patients with peak serum E2 < 4,000 pg/ml despite aggressive steroidal supplementation. It has been proposed that the use of adjuvant low dose hCG at the time of GnRH agonist trigger or 35 hours later will rescue some of the corpora lutea and help improve corpora lutea function and improve pregnancy rates.
The study will evaluate patients at high risk of OHSS development with peak serum E2 < 4,000 pg/mL to determine whether timing of low dose hCG administration affects ongoing pregnancy rates or risk of OHSS. Markers of corpus luteum function such as serum 17 hydroxy-progesterone and prorenin during the luteal phase and early pregnancy will help elucidate further the effect of adjuvant low dose hCG with GnRH agonist trigger on corpus luteum function.
- Conditions
- Ovarian Hyperstimulation Syndrome
- Being tested
- hCG
- Keywords
- OHSS, GnRH agonist trigger, low dose hCG, PCOS, IVF
- Medical subject headings
- Ovarian Hyperstimulation Syndrome, Polycystic Ovary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hCGDrug
Also called Pregnyl, Profasi
Adjuvant low dose hCG 1,000 IU administered at the time of GnRH agonist trigger
hCGDrug
Also called Pregnyl, Profasi
Adjuvant low dose hCG 1,500 IU administered 35 hours after GnRH agonist trigger
| Study group | Role | What they receive |
|---|---|---|
| hCG given at time of GnRHa trigger | Experimental | Adjuvant low dose hCG 1,000 IU administered at the time of GnRH agonist trigger.
Placebo administered 35 hours after GnRH agonist trigger Receives: Drug: hCG |
| hCG given 35 hours after GnRHa trigger | Active comparator | Placebo administered at the time of GnRH agonist trigger
Adjuvant low dose hCG 1,500 IU administered 35 hours after GnRH agonist trigger. Receives: Drug: hCG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ongoing Pregnancy
Positive serum pregnancy test and ultrasound evidence of fetal pole and fetal heart rate .
Measured: Through time of study completion, on average 1-2years
Secondary outcomes (1)
Ovarian Hyperstimulation Syndrome
Evaluation of symptoms and signs of OHSS at 9 days after trigger of oocyte maturation. Patients who also present with symptoms of OHSS wil also be evaluated for OHSS within 4 weeks after oocyte maturation.
Measured: Within 4 weeks of oocyte retrieval
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2013 (estimated)
- Study startMar 2013
- Primary completionDec 2015
- Study completionOct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Ovarian Hyperstimulation SyndromeStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 89 participants (actual)
Sponsor and investigators
- Lead sponsor
- UConn Health
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Lawrence Engmann, UConn Health
- Investigators
- Lawrence Engmann, MD, Principal investigator, UConn Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01815138
- Sponsor's protocol ID
- 13-098-3
- Status last verified
- Sep 2018
- First submitted
- 16 Mar 2013
- Last updated
- 26 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Griffin D, Benadiva C, Kummer N, Budinetz T, Nulsen J, Engmann L. Dual trigger of oocyte maturation with gonadotropin-releasing hormone agonist and low-dose human chorionic gonadotropin to optimize live birth rates in high responders. Fertil Steril. 2012 Jun;97(6):1316-20. doi: 10.1016/j.fertnstert.2012.03.015. Epub 2012 Apr 3.
PubMed 22480822Kummer N, Benadiva C, Feinn R, Mann J, Nulsen J, Engmann L. Factors that predict the probability of a successful clinical outcome after induction of oocyte maturation with a gonadotropin-releasing hormone agonist. Fertil Steril. 2011 Jul;96(1):63-8. doi: 10.1016/j.fertnstert.2011.04.050. Epub 2011 May 12.
PubMed 21565337Engmann L, DiLuigi A, Schmidt D, Nulsen J, Maier D, Benadiva C. The use of gonadotropin-releasing hormone (GnRH) agonist to induce oocyte maturation after cotreatment with GnRH antagonist in high-risk patients undergoing in vitro fertilization prevents the risk of ovarian hyperstimulation syndrome: a prospective randomized controlled study. Fertil Steril. 2008 Jan;89(1):84-91. doi: 10.1016/j.fertnstert.2007.02.002. Epub 2007 Apr 26.
PubMed 17462639Humaidan P. Luteal phase rescue in high-risk OHSS patients by GnRHa triggering in combination with low-dose HCG: a pilot study. Reprod Biomed Online. 2009 May;18(5):630-4. doi: 10.1016/s1472-6483(10)60006-5.
PubMed 19549440Humaidan P, Bungum L, Bungum M, Yding Andersen C. Rescue of corpus luteum function with peri-ovulatory HCG supplementation in IVF/ICSI GnRH antagonist cycles in which ovulation was triggered with a GnRH agonist: a pilot study. Reprod Biomed Online. 2006 Aug;13(2):173-8. doi: 10.1016/s1472-6483(10)60612-8.
PubMed 16895629Kaye L, Griffin D, Thorne J, Neuber E, Nulsen J, Benadiva C, Engmann L. Independent serum markers of corpora lutea function after gonadotropin-releasing hormone agonist trigger and adjuvant low dose human chorionic gonadotropin in in vitro fertilization. Fertil Steril. 2019 Sep;112(3):534-544. doi: 10.1016/j.fertnstert.2019.04.034. Epub 2019 Jun 18.
PubMed 31227286
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Double-blind Randomized Trial Comparing Pregnancy Rates After Low Dose Human Chorionic Gonadotropin (hCG) at the Time of Gonadotropin Releasing Hormone (GnRH) Agonist Trigger or 35 Hours Later for the Prevention of OHSS
- ClinicalTrials.gov ID
- NCT01815138
- Acronym / sponsor ID
- 13-098-3
- Conditions
- Ovarian Hyperstimulation Syndrome
- Keywords
- OHSS, GnRH agonist trigger, low dose hCG, PCOS, IVF
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 89 participants (actual)
- Lead sponsor
- UConn HealthUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Mar 2013
- Primary completion
- Dec 2015 (actual)
- Study completion
- Oct 2016 (actual)
- First posted
- 20 Mar 2013 (estimated)
- Results
- Posted 25 Sep 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This a prospective randomized double blind study involving patients at high risk of OHSS development with peak serum E2 levels < 4,000 pg/ml comparing the ongoing pregnancy rates in patients who receive adjuvant hCG 1,000 IU at the time of GnRH agonist trigger or adjuvant hCG 1,500 IU 35 hours after GnRH agonist trigger.
Detailed description
Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of controlled ovarian hyperstimulation which may result in significant morbidity and rarely mortality as well as significant financial and psychological distress. GnRH agonist trigger has been shown to be effective in OHSS prevention. However, the adoption of its use has not been widely accepted in view of concerns regarding potential impairment of implantation.
Intensive luteal phase supplementation with estrogen (E2) and progesterone (P) is important due to the strong evidence of abnormal luteal phase serum E2 and P profiles. However, it has been shown that optimal conception rates is not achieved for high risk patients with peak serum E2 < 4,000 pg/ml despite aggressive steroidal supplementation. It has been proposed that the use of adjuvant low dose hCG at the time of GnRH agonist trigger or 35 hours later will rescue some of the corpora lutea and help improve corpora lutea function and improve pregnancy rates.
The study will evaluate patients at high risk of OHSS development with peak serum E2 < 4,000 pg/mL to determine whether timing of low dose hCG administration affects ongoing pregnancy rates or risk of OHSS. Markers of corpus luteum function such as serum 17 hydroxy-progesterone and prorenin during the luteal phase and early pregnancy will help elucidate further the effect of adjuvant low dose hCG with GnRH agonist trigger on corpus luteum function.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| hCG given at time of GnRHa trigger | Experimental | Drug: hCGAdjuvant low dose hCG 1,000 IU administered at the time of GnRH agonist trigger. Placebo administered 35 hours after GnRH agonist trigger |
| hCG given 35 hours after GnRHa trigger | Active comparator | Drug: hCGPlacebo administered at the time of GnRH agonist trigger Adjuvant low dose hCG 1,500 IU administered 35 hours after GnRH agonist trigger. |
Who may qualify
- Ages
- 18 to 39 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Normal baseline serum follicle stimulating hormone, polycystic ovarian syndrome (PCOS), Polycystic ovarian morphology, Previous high responder or previous OHSS, must have > 14 follicles of over 11 mm in diameter and with peak serum E2 levels < 4,000 pg/mL on the day of trigger of oocyte maturation.
Key exclusion criteria (1 listed)
- Hypothalamic dysfunction, Patients with < 14 follicles < 11 mm in diameter, peak serum E2 levels >= 4,000 pg/mL.
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 |
|---|---|---|
| hCGAlso: Pregnyl, ProfasiAdjuvant low dose hCG 1,000 IU administered at the time of GnRH agonist trigger | Drug | hCG given at time of GnRHa trigger |
| hCGAlso: Pregnyl, ProfasiAdjuvant low dose hCG 1,500 IU administered 35 hours after GnRH agonist trigger | Drug | hCG given 35 hours after GnRHa trigger |
Primary outcome
Ongoing Pregnancy
Time frame: Through time of study completion, on average 1-2years
Positive serum pregnancy test and ultrasound evidence of fetal pole and fetal heart rate .
1 secondary outcome
Ovarian Hyperstimulation Syndrome
Time frame: Within 4 weeks of oocyte retrieval
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22480822Griffin D, Benadiva C, Kummer N, Budinetz T, Nulsen J, Engmann L. Dual trigger of oocyte maturation with gonadotropin-releasing hormone agonist and low-dose human chorionic gonadotropin to optimize live birth rates in high responders. Fertil Steril. 2012 Jun;97(6):1316-20. doi: 10.1016/j.fertnstert.2012.03.015. Epub 2012 Apr 3.
- Background: PubMed 21565337Kummer N, Benadiva C, Feinn R, Mann J, Nulsen J, Engmann L. Factors that predict the probability of a successful clinical outcome after induction of oocyte maturation with a gonadotropin-releasing hormone agonist. Fertil Steril. 2011 Jul;96(1):63-8. doi: 10.1016/j.fertnstert.2011.04.050. Epub 2011 May 12.
- Background: PubMed 17462639Engmann L, DiLuigi A, Schmidt D, Nulsen J, Maier D, Benadiva C. The use of gonadotropin-releasing hormone (GnRH) agonist to induce oocyte maturation after cotreatment with GnRH antagonist in high-risk patients undergoing in vitro fertilization prevents the risk of ovarian hyperstimulation syndrome: a prospective randomized controlled study. Fertil Steril. 2008 Jan;89(1):84-91. doi: 10.1016/j.fertnstert.2007.02.002. Epub 2007 Apr 26.
- Background: PubMed 19549440Humaidan P. Luteal phase rescue in high-risk OHSS patients by GnRHa triggering in combination with low-dose HCG: a pilot study. Reprod Biomed Online. 2009 May;18(5):630-4. doi: 10.1016/s1472-6483(10)60006-5.
- Background: PubMed 16895629Humaidan P, Bungum L, Bungum M, Yding Andersen C. Rescue of corpus luteum function with peri-ovulatory HCG supplementation in IVF/ICSI GnRH antagonist cycles in which ovulation was triggered with a GnRH agonist: a pilot study. Reprod Biomed Online. 2006 Aug;13(2):173-8. doi: 10.1016/s1472-6483(10)60612-8.
- Derived from this study: PubMed 31227286Kaye L, Griffin D, Thorne J, Neuber E, Nulsen J, Benadiva C, Engmann L. Independent serum markers of corpora lutea function after gonadotropin-releasing hormone agonist trigger and adjuvant low dose human chorionic gonadotropin in in vitro fertilization. Fertil Steril. 2019 Sep;112(3):534-544. doi: 10.1016/j.fertnstert.2019.04.034. Epub 2019 Jun 18.
- Individual participant dataSharing planned: Undecided
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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.
Lawrence Engmann, MD principal investigator
UConn Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing hCG in people with Ovarian Hyperstimulation Syndrome, run by UConn Health at 1 site in United States.
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 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 26 Oct 2018. 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 United States. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 (time frame: Through time of study completion, on average 1-2years). 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 NCT01815138, which also lists 6 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 26 Oct 2018.