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Co-administration of Low Dose hCG at the Time of GnRH Agonist Trigger or 35 Hours Later for the Prevention of OHSS

Primary Purpose

Ovarian Hyperstimulation Syndrome

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
hCG
hCG
Sponsored by
UConn Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Hyperstimulation Syndrome focused on measuring OHSS, GnRH agonist trigger, low dose hCG, PCOS, IVF

Eligibility Criteria

18 Years - 39 Years (Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • Hypothalamic dysfunction, Patients with < 14 follicles < 11 mm in diameter, peak serum E2 levels >= 4,000 pg/mL.

Sites / Locations

  • University of Connecticut Health Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

hCG given at time of GnRHa trigger

hCG given 35 hours after GnRHa trigger

Arm Description

Adjuvant low dose hCG 1,000 IU administered at the time of GnRH agonist trigger. Placebo administered 35 hours after GnRH agonist trigger

Placebo administered at the time of GnRH agonist trigger Adjuvant low dose hCG 1,500 IU administered 35 hours after GnRH agonist trigger.

Outcomes

Primary Outcome Measures

Ongoing Pregnancy
Positive serum pregnancy test and ultrasound evidence of fetal pole and fetal heart rate .

Secondary Outcome Measures

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.

Full Information

First Posted
March 16, 2013
Last Updated
September 25, 2018
Sponsor
UConn Health
Collaborators
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT01815138
Brief Title
Co-administration of Low Dose hCG at the Time of GnRH Agonist Trigger or 35 Hours Later for the Prevention of OHSS
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
March 2013 (undefined)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
October 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
UConn Health
Collaborators
Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Hyperstimulation Syndrome
Keywords
OHSS, GnRH agonist trigger, low dose hCG, PCOS, IVF

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
89 (Actual)

8. Arms, Groups, and Interventions

Arm Title
hCG given at time of GnRHa trigger
Arm Type
Experimental
Arm Description
Adjuvant low dose hCG 1,000 IU administered at the time of GnRH agonist trigger. Placebo administered 35 hours after GnRH agonist trigger
Arm Title
hCG given 35 hours after GnRHa trigger
Arm Type
Active Comparator
Arm Description
Placebo administered at the time of GnRH agonist trigger Adjuvant low dose hCG 1,500 IU administered 35 hours after GnRH agonist trigger.
Intervention Type
Drug
Intervention Name(s)
hCG
Other Intervention Name(s)
Pregnyl, Profasi
Intervention Description
Adjuvant low dose hCG 1,000 IU administered at the time of GnRH agonist trigger
Intervention Type
Drug
Intervention Name(s)
hCG
Other Intervention Name(s)
Pregnyl, Profasi
Intervention Description
Adjuvant low dose hCG 1,500 IU administered 35 hours after GnRH agonist trigger
Primary Outcome Measure Information:
Title
Ongoing Pregnancy
Description
Positive serum pregnancy test and ultrasound evidence of fetal pole and fetal heart rate .
Time Frame
Through time of study completion, on average 1-2years
Secondary Outcome Measure Information:
Title
Ovarian Hyperstimulation Syndrome
Description
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.
Time Frame
Within 4 weeks of oocyte retrieval
Other Pre-specified Outcome Measures:
Title
Markers of Corpus Luteum Function
Description
A subset of patients (20 patients in each group) will have serum frozen for subsequent analysis of 17 hydroxy progesterone and prorenin.
Time Frame
Within 60 days after trigger of oocyte maturation
Title
Proportion of Patients With Abdominal Distension
Description
Patients will complete a questionnaire to determine if there is a difference in the effect of the intervention on the quality of life (abdominal distension) of the patients from the day of trigger of oocyte maturation until menses or positive pregnancy test.
Time Frame
Within 2 weeks after trigger of oocyte maturation

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
39 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: Hypothalamic dysfunction, Patients with < 14 follicles < 11 mm in diameter, peak serum E2 levels >= 4,000 pg/mL.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lawrence Engmann, MD
Organizational Affiliation
UConn Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Connecticut Health Center
City
Farmington
State/Province
Connecticut
ZIP/Postal Code
06030
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
22480822
Citation
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.
Results Reference
background
PubMed Identifier
21565337
Citation
Kummer 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.
Results Reference
background
PubMed Identifier
17462639
Citation
Engmann 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.
Results Reference
background
PubMed Identifier
19549440
Citation
Humaidan 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.
Results Reference
background
PubMed Identifier
16895629
Citation
Humaidan 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.
Results Reference
background
PubMed Identifier
31227286
Citation
Kaye 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.
Results Reference
derived

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Co-administration of Low Dose hCG at the Time of GnRH Agonist Trigger or 35 Hours Later for the Prevention of OHSS

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