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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| hCG | Drug | Adjuvant low dose hCG 1,000 IU administered at the time of GnRH agonist trigger |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Proportion of Patients With Abdominal Distension |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Lawrence Engmann, MD | UConn Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Connecticut Health Center | Farmington | Connecticut | 06030 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22480822 | Background | 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. | |
| 21565337 |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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 |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | hCG Given 35 Hours After GnRHa Trigger |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Ongoing Pregnancy | Positive serum pregnancy test and ultrasound evidence of fetal pole and fetal heart rate . | per protocol analysis | Posted | Number | participants | Through time of study completion, on average 1-2years |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ectopic Pregnancy | Pregnancy, puerperium and perinatal conditions | Systematic Assessment | Patient diagnosed with un-ruptured ectopic pregnancy and required a laparoscopy |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Lawrence Engmann | UConn Helth | 8605258283 | lengmann@uchc.edu |
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| ID | Term |
|---|---|
| D016471 | Ovarian Hyperstimulation Syndrome |
| D011085 | Polycystic Ovary Syndrome |
| ID | Term |
|---|---|
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
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| ID | Term |
|---|---|
| D006063 | Chorionic Gonadotropin |
| C412829 | Profasi |
| ID | Term |
|---|---|
| D006062 | Gonadotropins |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
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| hCG | Drug | Adjuvant low dose hCG 1,500 IU administered 35 hours after GnRH agonist trigger |
|
|
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 |
| 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. |
| 17462639 | Background | 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. |
| 19549440 | Background | 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. |
| 16895629 | Background | 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. |
| 31227286 | Derived | 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. |
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 |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | "kg/m^2" |
|
| Anti Mullerian Hormone (AMH) | Mean | Standard Deviation | ng/ml |
|
| Follicle Stimulating Hormone (FSH) | Mean | Standard Deviation | IU/L |
|
|
|
| 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. | Women with normal or high response to IVF, peak estradiol on day of trigger less than 4000 pg/mL. | Posted | Count of Participants | Participants | Within 4 weeks of oocyte retrieval |
|
|
|
|
| Other Pre-specified | 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. | Subset of women included in larger study, normal or high responders, peak estradiol level less than 4000 pg/mL on day of trigger. | Posted | Mean | Standard Deviation | ng/mL | Within 60 days after trigger of oocyte maturation |
|
|
|
|
| Other Pre-specified | 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. | Some patients did not complete the questionnaire. Abdominal distension analyzed | Posted | Count of Participants | Participants | Within 2 weeks after trigger of oocyte maturation |
|
|
|
| 0 |
| 26 |
| 1 |
| 26 |
| 0 |
| 26 |
| EG001 | 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 | 0 | 31 | 1 | 31 | 0 | 31 |
|
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| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D006058 | Gonadal Disorders |
| D004700 | Endocrine System Diseases |
| D010048 | Ovarian Cysts |
| D003560 | Cysts |
| D009369 | Neoplasms |
| D010926 | Placental Hormones |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011257 | Pregnancy Proteins |
| D011506 | Proteins |