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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ClinicalTrials.gov Identifier: NCT01815138

Recruitment Status : Completed

First Posted : March 20, 2013

Results First Posted : September 25, 2017

Last Update Posted : October 26, 2018

Sponsor:

Collaborator:

Merck Sharp & Dohme Corp.

Information provided by (Responsible Party):

Lawrence Engmann, UConn Health

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.

Condition or disease	Intervention/treatment	Phase
Ovarian Hyperstimulation Syndrome	Drug: hCG	Phase 4

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

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	89 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
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 Start Date :	March 2013
Actual Primary Completion Date :	December 2015
Actual Study Completion Date :	October 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pregnancy

Drug Information available for: Chorionic Gonadotropin Choriogonadotropin Alfa

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: hCG given at time of GnRHa trigger Adjuvant low dose hCG 1,000 IU administered at the time of GnRH agonist trigger. Placebo administered 35 hours after GnRH agonist trigger	Drug: hCG Adjuvant low dose hCG 1,000 IU administered at the time of GnRH agonist trigger Other Name: Pregnyl, Profasi
Active Comparator: hCG given 35 hours after GnRHa trigger Placebo administered at the time of GnRH agonist trigger Adjuvant low dose hCG 1,500 IU administered 35 hours after GnRH agonist trigger.	Drug: hCG Adjuvant low dose hCG 1,500 IU administered 35 hours after GnRH agonist trigger Other Name: Pregnyl, Profasi

Outcome Measures

Primary Outcome Measures :

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 .

Secondary Outcome Measures :

Ovarian Hyperstimulation Syndrome [ Time Frame: Within 4 weeks of oocyte retrieval ]
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.

Other Outcome Measures:

Markers of Corpus Luteum Function [ Time Frame: Within 60 days after trigger of oocyte maturation ]
A subset of patients (20 patients in each group) will have serum frozen for subsequent analysis of 17 hydroxy progesterone and prorenin.
Proportion of Patients With Abdominal Distension [ Time Frame: Within 2 weeks after trigger of oocyte maturation ]
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.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years to 39 Years (Adult)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01815138

Locations

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United States, Connecticut
University of Connecticut Health Center
Farmington, Connecticut, United States, 06030

Sponsors and Collaborators

UConn Health

Merck Sharp & Dohme Corp.

Investigators

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Principal Investigator:	Lawrence Engmann, MD	UConn Health

More Information

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.

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.

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. Epub 2007 Apr 26.

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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Responsible Party:	Lawrence Engmann, MD, UConn Health
ClinicalTrials.gov Identifier:	NCT01815138
Other Study ID Numbers:	13-098-3
First Posted:	March 20, 2013 Key Record Dates
Results First Posted:	September 25, 2017
Last Update Posted:	October 26, 2018
Last Verified:	September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

Keywords provided by Lawrence Engmann, UConn Health:


OHSS, GnRH agonist trigger, low dose hCG, PCOS, IVF

Additional relevant MeSH terms:

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Ovarian Hyperstimulation Syndrome Ovarian Diseases Adnexal Diseases Gonadal Disorders	Endocrine System Diseases Chorionic Gonadotropin Reproductive Control Agents Physiological Effects of Drugs

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