Trial Outcomes & Findings for Co-administration of Low Dose hCG at the Time of GnRH Agonist Trigger or 35 Hours Later for the Prevention of OHSS (NCT NCT01815138)

NCT ID: NCT01815138

Last Updated: 2018-10-26

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 89 participants
• Primary outcome timeframe: Through time of study completion, on average 1-2years
• Results posted on: 2018-10-26

Participant Flow

All patients that met initial study criteria were enrolled and consented before starting ovarian stimulation. Final randomization occurred during stimulation. Therefore patients who were enrolled and consented may drop out before randomization, either because they did not meet the final inclusion criteria in did not undergo IVF.

Participant milestones

Measure	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 hCG: Adjuvant low dose hCG 1,000 IU administered at the time of GnRH agonist trigger	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. hCG: Adjuvant low dose hCG 1,500 IU administered 35 hours after GnRH agonist trigger
Overall Study STARTED	34	37
Overall Study COMPLETED	26	31
Overall Study NOT COMPLETED	8	6

Reasons for withdrawal

Measure	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 hCG: Adjuvant low dose hCG 1,000 IU administered at the time of GnRH agonist trigger	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. hCG: Adjuvant low dose hCG 1,500 IU administered 35 hours after GnRH agonist trigger
Overall Study Withdrawal by Subject	0	1
Overall Study Physician Decision	8	5

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	hCG Given at Time of GnRHa Trigger n=26 Participants Adjuvant low dose hCG 1,000 IU administered at the time of GnRH agonist trigger. Placebo administered 35 hours after GnRH agonist trigger hCG: Adjuvant low dose hCG 1,000 IU administered at the time of GnRH agonist trigger	hCG Given 35 Hours After GnRHa Trigger n=31 Participants Placebo administered at the time of GnRH agonist trigger Adjuvant low dose hCG 1,500 IU administered 35 hours after GnRH agonist trigger. hCG: Adjuvant low dose hCG 1,500 IU administered 35 hours after GnRH agonist trigger	Total n=57 Participants Total of all reporting groups
Sex: Female, Male Male	0 Participants n=26 Participants	0 Participants n=31 Participants	0 Participants n=57 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Body Mass Index (BMI)	26.3 "kg/m^2" STANDARD_DEVIATION 4.8 • n=26 Participants	27.4 "kg/m^2" STANDARD_DEVIATION 5.5 • n=31 Participants	26.9 "kg/m^2" STANDARD_DEVIATION 5.2 • n=57 Participants
Anti Mullerian Hormone (AMH)	8.3 ng/ml STANDARD_DEVIATION 5.8 • n=26 Participants	8.4 ng/ml STANDARD_DEVIATION 4.9 • n=31 Participants	8.35 ng/ml STANDARD_DEVIATION 5.2 • n=57 Participants
Age, Continuous	31.3 years STANDARD_DEVIATION 3.3 • n=26 Participants	32.2 years STANDARD_DEVIATION 3.4 • n=31 Participants	31.8 years STANDARD_DEVIATION 3.4 • n=57 Participants
Sex: Female, Male Female	26 Participants n=26 Participants	31 Participants n=31 Participants	57 Participants n=57 Participants
Follicle Stimulating Hormone (FSH)	5.6 IU/L STANDARD_DEVIATION 1.7 • n=26 Participants	5.2 IU/L STANDARD_DEVIATION 1.6 • n=31 Participants	5.5 IU/L STANDARD_DEVIATION 2.1 • n=57 Participants

PRIMARY outcome

Timeframe: Through time of study completion, on average 1-2years

Population: per protocol analysis

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

Outcome measures

Measure	hCG Given at Time of GnRHa Trigger n=26 Participants Adjuvant low dose hCG 1,000 IU administered at the time of GnRH agonist trigger. Placebo administered 35 hours after GnRH agonist trigger hCG: Adjuvant low dose hCG 1,000 IU administered at the time of GnRH agonist trigger	hCG Given 35 Hours After GnRHa Trigger n=31 Participants Placebo administered at the time of GnRH agonist trigger Adjuvant low dose hCG 1,500 IU administered 35 hours after GnRH agonist trigger. hCG: Adjuvant low dose hCG 1,500 IU administered 35 hours after GnRH agonist trigger
Ongoing Pregnancy	15 participants	19 participants

SECONDARY outcome

Timeframe: Within 4 weeks of oocyte retrieval

Population: Women with normal or high response to IVF, peak estradiol on day of trigger less than 4000 pg/mL.

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.

Outcome measures

Measure	hCG Given at Time of GnRHa Trigger n=26 Participants Adjuvant low dose hCG 1,000 IU administered at the time of GnRH agonist trigger. Placebo administered 35 hours after GnRH agonist trigger hCG: Adjuvant low dose hCG 1,000 IU administered at the time of GnRH agonist trigger	hCG Given 35 Hours After GnRHa Trigger n=31 Participants Placebo administered at the time of GnRH agonist trigger Adjuvant low dose hCG 1,500 IU administered 35 hours after GnRH agonist trigger. hCG: Adjuvant low dose hCG 1,500 IU administered 35 hours after GnRH agonist trigger
Ovarian Hyperstimulation Syndrome	1 Participants	3 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Within 60 days after trigger of oocyte maturation

Population: Subset of women included in larger study, normal or high responders, peak estradiol level less than 4000 pg/mL on day of trigger.

A subset of patients (20 patients in each group) will have serum frozen for subsequent analysis of 17 hydroxy progesterone and prorenin.

Outcome measures

Measure	hCG Given at Time of GnRHa Trigger n=10 Participants Adjuvant low dose hCG 1,000 IU administered at the time of GnRH agonist trigger. Placebo administered 35 hours after GnRH agonist trigger hCG: Adjuvant low dose hCG 1,000 IU administered at the time of GnRH agonist trigger	hCG Given 35 Hours After GnRHa Trigger n=20 Participants Placebo administered at the time of GnRH agonist trigger Adjuvant low dose hCG 1,500 IU administered 35 hours after GnRH agonist trigger. hCG: Adjuvant low dose hCG 1,500 IU administered 35 hours after GnRH agonist trigger
Markers of Corpus Luteum Function Early luteal 17-OH-Progesterone	13.68 ng/mL Standard Deviation 11.0	21.77 ng/mL Standard Deviation 8.5
Markers of Corpus Luteum Function Day 16 Prorenin	1.13 ng/mL Standard Deviation 0.8	2.22 ng/mL Standard Deviation 1.6

OTHER_PRE_SPECIFIED outcome

Timeframe: Within 2 weeks after trigger of oocyte maturation

Population: Some patients did not complete the questionnaire. Abdominal distension analyzed

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.

Outcome measures

Measure	hCG Given at Time of GnRHa Trigger n=20 Participants Adjuvant low dose hCG 1,000 IU administered at the time of GnRH agonist trigger. Placebo administered 35 hours after GnRH agonist trigger hCG: Adjuvant low dose hCG 1,000 IU administered at the time of GnRH agonist trigger	hCG Given 35 Hours After GnRHa Trigger n=27 Participants Placebo administered at the time of GnRH agonist trigger Adjuvant low dose hCG 1,500 IU administered 35 hours after GnRH agonist trigger. hCG: Adjuvant low dose hCG 1,500 IU administered 35 hours after GnRH agonist trigger
Proportion of Patients With Abdominal Distension Abdominal distension	2 Participants	11 Participants
Proportion of Patients With Abdominal Distension abdominal pain	1 Participants	9 Participants

Adverse Events

hCG Given at Time of GnRHa Trigger

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

hCG Given 35 Hours After GnRHa Trigger

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	hCG Given at Time of GnRHa Trigger n=26 participants at risk Adjuvant low dose hCG 1,000 IU administered at the time of GnRH agonist trigger. Placebo administered 35 hours after GnRH agonist trigger hCG: Adjuvant low dose hCG 1,000 IU administered at the time of GnRH agonist trigger	hCG Given 35 Hours After GnRHa Trigger n=31 participants at risk Placebo administered at the time of GnRH agonist trigger Adjuvant low dose hCG 1,500 IU administered 35 hours after GnRH agonist trigger. hCG: Adjuvant low dose hCG 1,500 IU administered 35 hours after GnRH agonist trigger
Pregnancy, puerperium and perinatal conditions Ectopic Pregnancy	3.8% 1/26 • Number of events 1	3.2% 1/31 • Number of events 1

Other adverse events

Adverse event data not reported

Additional Information

Lawrence Engmann

UConn Helth

Phone: 8605258283

Email: lengmann@uchc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place