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

Ovarian Hyperstimulation Syndrome Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01815138
• Other study ID #: 13-098-3
• Status: Completed
• Phase: Phase 4
• Start date: March 2013
• Est. completion date: October 2016

Study information

• Verified date: September 2018
• Source: UConn Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 trigger.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 89
• Est. completion date: October 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 39 Years

Eligibility

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.

Related Conditions & MeSH terms

• Ovarian Hyperstimulation Syndrome

Intervention

Drug:
• hCG
Adjuvant low dose hCG 1,000 IU administered at the time of GnRH agonist trigger
• hCG
Adjuvant low dose hCG 1,500 IU administered 35 hours after GnRH agonist trigger

Locations

Country	Name	City	State
United States	University of Connecticut Health Center	Farmington	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
UConn Health	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Markers of Corpus Luteum Function	A subset of patients (20 patients in each group) will have serum frozen for subsequent analysis of 17 hydroxy progesterone and prorenin.	Within 60 days after trigger of oocyte maturation
Other	Proportion of Patients With Abdominal Distension	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.	Within 2 weeks after trigger of oocyte maturation
Primary	Ongoing Pregnancy	Positive serum pregnancy test and ultrasound evidence of fetal pole and fetal heart rate .	Through time of study completion, on average 1-2years
Secondary	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.	Within 4 weeks of oocyte retrieval