Clinical trial NCT03073980
Conditions: Infertility, Female Pain, Postoperative
Keywords: in vitro fertilization oocyte retrieval acetaminophen postoperative pain control
Sponsor: Massachusetts General Hospital
Start date: 2019-09-01; Completion date: 2020-12-01
Enrollment: 161 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
In this research study we want to learn more about how effective certain medications are at reducing pain after oocyte (egg) retrieval surgery and how effective they are at reducing the time between the retrieval and discharge from the hospital. We will compare three types of pre-operative medications: intravenous (IV) acetaminophen, oral (PO) acetaminophen, and placebo (no medication), which is the current typical care.

Detailed description:
OBJECTIVE: To compare the efficacy of pre-operative IV acetaminophen, PO acetaminophen, versus placebo for adjunctive pain control in the setting of oocyte retrieval in an in vitro fertilization clinic setting.

HYPOTHESIS: Our hypothesis is that patients receiving IV acetaminophen pre-operatively will have improved postoperative pain scores, lower overall opiate consumption, and shortened time to discharge from post analgesic recovery unit (PACU) or recovery than those receiving PO acetaminophen or placebo.

Participants will be consented and enrolled in the study prior to their oocyte retrieval. The patient will then be randomized to one of three treatments:

Group 1: In the pre-op suite, these patients will receive 1000mg IV acetaminophen and PO placebo, followed by standard protocol anesthesia and pain control as needed.

Group 2: In the pre-op suite, these patients will receive 1000mg PO acetaminophen and IV placebo, followed by standard protocol anesthesia and pain control as needed.

Group 3:

In the pre-op suite, these patients will receive PO and IV placebo, followed by standard protocol anesthesia and pain control as needed.

The patient and care team will be blinded to the treatment group.

A member of the study staff will review participants' medical record to collect data regarding demographics, clinical history, cycle and pregnancy outcomes, up to 12 months following study completion.

Arms: arm 1: In the pre-operative suite, these patients will receive 1000mg IV acetaminophen and PO placebo, followed by standard protocol anesthesia and pain control as needed. arm 2: In the pre-op suite, these patients will receive 1000mg PO acetaminophen and IV placebo, followed by standard protocol anesthesia and pain control as needed. arm 3: In the pre-op suite, these patients will receive PO and IV placebo, followed by standard protocol anesthesia and pain control as needed.
Interventions: intervention 1: IV Acetaminophen intervention 2: PO Acetaminophen intervention 3: Placebo IV Acetaminophen intervention 4: Placebo PO Acetaminophen
Intervention descriptions: intervention 1: IV Acetaminophen for pain control during procedure intervention 2: PO Acetaminophen for pain control during procedure intervention 3: Placebo IV Acetaminophen intervention 4: Placebo PO Acetaminophen

Protocol documents:
Prot_SAP_000.pdf: 
 
 
1 
DETAILED PROTOCOL 
 
Assessing efficacy of IV acetaminophen for perioperative pain control for oocyte retrieval: a 
randomized, double blind, placebo-controlled trial 
 
Principal Investigator: John C. Petrozza, MD 
Version Date: July 10, 2019 
 
I. BACKGROUND AND SIGNIFICANCE 
 
a. Historical background 
 
Due to the current opioid crisis, non-opioid options for effective multimodal postoperative 
anesthesia have been explored in many recent studies. Intravenous acetaminophen has rapid 
onset and potent analgesic properties, but due to its high cost and relatively limited clinical data 
concerning its efficacy compared with other agents, physicians are hesitant to use intravenous 
acetaminophen in the perioperative period. Importantly, for minor outpatient procedures such as 
oocyte retrievals, use of IV acetaminophen offers the opportunity to greatly reduce perioperative 
narcotic intake in women of reproductive age. 
 
b. Previous pre-/clinical studies supporting the proposed research 
 
Postoperative pain 
The majority of postoperative patients experience moderate to severe postsurgical pain, which 
can lead to complications such as impaired wound healing.1,2 Although we rely heavily on 
opioids to alleviate much of postoperative pain, this analgesia is not without adverse effects. 
Opioids are associated with drowsiness, postoperative nausea and vomiting, ileus, respiratory 
depression, and bladder dysfunction, all of which can hamper post-operative recovery and 
discharge.3 Thus, as we attempt across surgical specialties to reduce the use of opiates for 
outpatient procedures, IV acetaminophen is an important consideration for multimodal 
anesthesia for oocyte retrievals.4 
 
Safety of IV acetaminophen 
Although IV acetaminophen is more expensive than PO acetaminophen and less likely to be fully 
reimbursed by insurance companies, there is evidence that favors the intravenous formulation 
over the oral agent. The bioavailability of IV acetaminophen in cerebrospinal fluid compared 
with oral acetaminophen after the administration of 1 gram over 6 hours is 24.9 versus 14.2 
μg•hr/mL.5 IV acetaminophen produces more consistent plasma concentrations of 
acetaminophen over time than PO administration, leading to a longer duration of therapeutic 
drug plasma level.1 The intravenous route also peaks much faster (15 minutes vs. 45 minutes).1 
Though the risk for overdose always exists, there is evidence that IV acetaminophen may be 
safer than the same dose of PO acetaminophen: IV administration creates a lower accumulation 
of acetaminophen’s toxic metabolite (n-acetyl-p-benzoquinoneimine) than oral administration 
and produces a peak acetaminophen concentration in the liver estimated to be 50% less than the 
same oral dose.6  
 


 
 
2 
IV acetaminophen for postsurgical analgesia 
A recent review of 14 randomized controlled trials examining the efficacy of IV acetaminophen 
for postoperative pain in a wide variety of surgeries found that patients receiving IV 
acetaminophen had improved analgesia in 12 of the studies examined.7 Sinatra et al. showed that 
IV acetaminophen use (one gram every six hours) was associated with a decrease in morphine 
consumption by 46% (p=0.0003) on postoperative day one after total hip replacement or total 
knee replacement and increased time until rescue morphine (hip replacement, 3.9 hours and knee 
replacement, 2.1 hours) compared with placebo (0.8 hours).8 Other studies in hysterectomy and 
laminectomy patients suggest that patients receiving IV acetaminophen may have a reduction in 
postoperative nausea and vomiting, although this has yet to be formally evaluated.7 Furthermore, 
both preemptive (before surgical incision) and preventive (after surgical incision) use of IV 
acetaminophen appears to produce a decrease in pain scores 6 hours after surgery compared with 
placebo (p<0.001).9 Therefore, the available evidence suggests that the addition of IV 
acetaminophen can bolster effective analgesia in patients while decreasing the amount of opioids 
required.2,3,9,10 
 
c. Rationale behind the proposed research, and potential benefits to patients 
and/or society. 
 
The use of IV acetaminophen is approved by the Food and Drug Administration for the 
management of mild to moderate pain, the management of moderate to severe pain with opioid 
analgesic adjuncts, and fever reduction in adults and children over the age of 2.11 As discussed 
above, recent studies have shown several benefits of using IV acetaminophen perioperatively, 
including a reduction in opiate consumption, improved analgesia, and reduced postoperative 
nausea and vomiting.3,10 While the cost effectiveness of using IV acetaminophen has not been 
extensively evaluated in surgical patients, a randomized controlled trial of bariatric surgery 
patients suggests that IV acetaminophen significantly decreases mean direct hospital costs and 
emergency department visits within 30 days of surgery.12 However, more research is needed to 
better assess the efficacy of IV acetaminophen compared to PO acetaminophen in treating 
postoperative pain and to further evaluate the potential reduction in opioid use. 
 
In our field, recent attention has focused on prescribing practices after oocyte retrievals as many 
opiate addictions begin with prescription medications.13,14 However, there are no studies to our 
knowledge assessing multimodal options for optimal pain control in the perioperative period, 
which may also impact the perceived need for pain medication prescriptions. Additionally, since 
cost is one of the limiting factors for giving patients IV acetaminophen, studies like this one that 
compare IV acetaminophen to oral acetaminophen and assess the impact on time to PACU 
discharge in both inpatient and outpatient settings are warranted. Our primary goal is to assess 
the efficacy of pre-operative IV versus PO Acetaminophen compared to placebo (standard of 
care) for pain control after oocyte retrieval, with the hypothesis that IV acetaminophen will 
reduce pain scores, reduce overall narcotic burden, shorten time to discharge from PACU, 
increase time to rescue medication, and decrease opiate-associated side effects. 
 
Investigating the use of non-opiate alternatives for perioperative anesthesia is a crucial aspect of 
reducing the overall use of opiates in outpatient procedures. IV acetaminophen has the potential 


 
 
3 
to be a versatile and worthwhile addition to achieving adequate postoperative analgesia in 
patients undergoing a wide variety of surgical procedures and in numerous hospital settings. 
 
II. SPECIFIC AIMS 
 
a. Specify objective and hypotheses to be tested in the project 
 
Objective: 
- To compare the efficacy of pre-operative IV acetaminophen versus PO acetaminophen, versus 
placebo (standard of care) for adjunctive pain control in the setting of oocyte retrieval in an in 
vitro fertilization clinic setting. 
 
Hypothesis: 
- Our hypothesis is that patients receiving IV acetaminophen pre-operatively will have improved 
postoperative pain scores, lower overall opiate consumption, and shortened time to discharge 
from PACU than those receiving PO acetaminophen or placebo. 
 
III. RESEARCH DESIGN AND METHODS 
 
This randomized, double blind, placebo-controlled study will be conducted over approximately 
12 months at the MGH Fertility Center. Our goal recruitment is 174 patients to achieve statistical 
power for our primary outcomes. 
a. Inclusion/exclusion criteria. 
 
Inclusion Criteria: 
[ ] Patient is 18 years or over, undergoing oocyte retrieval. 
[ ] Patient is English-speaking. 
 
Exclusion criteria: 
[ ] Allergy to acetaminophen or opiates. 
[ ] Any history of liver disease, history of alcohol depending, or renal impairment as reported in 
the electronic health record. 
[ ] Any history chronic opiate use or chronic pain disorder as reported in the electronic health 
record. 
[ ] Weight less than 50kg as reported in the medical record. 
 
b. Source of subjects and recruitment methods. 
 
Adult patients from the reproductive endocrinology practice at MGH undergoing oocyte 
retrieval. Patients will be recruited at the time of their IVF cycle. 
 
IV. SUBJECT ENROLLMENT 
 
a. Methods of enrollment, including procedures for patient registration and/ 
or randomization 
 


 
 
4 
All patients will be offered the chance to enroll in the study by a licensed MD at the time of their 
baseline ultrasound (IVF cycle start). The licensed physician will introduce the study and provide 
an information packet containing the study recruitment letter and informed consent at that time. 
The patient will have the opportunity to opt out of the study at any time. Study staff will confirm 
patients’ study eligibility by telephone during the cycle and indicate their participation on their 
IVF cycle monitoring schedule if they are eligible. Consent will occur in person during the IVF 
cycle by a licensed MD (see below). 
 
When the enrolled patient’s egg retrieval is scheduled (two days in advance of procedure), study 
staff will order the research medications in EPIC and will notify the IVF team and research 
pharmacy via secure email of the study patient’s procedure date/time to coordinate medication 
pick up. 
 
A computer-generated blocked randomization schema with alternating block sizes 
(http://www.randomization.com) will be generated by the research pharmacy. The fellow will 
enter a randomization number into the study patient’s EPIC medication order, and the pharmacist 
will associate this number to the patient’s assigned study group. The research pharmacist will 
prepare the appropriate medications, and the IVF care team will be blinded to the medications.  
 
b. Procedures for obtaining informed consent 
A licensed MD will consent the patient during one of their morning ultrasound appointments 
prior to the egg retrieval. It should be noted at the time of consent that participation in the study 
will in no way impact their infertility treatment or cycle management, that they will receive 
standard of care anesthesia, and that all perioperative pain will be treated. Consented patients 
must agree to avoid taking pain medications (including acetaminophen or NSAIDs) during the 
24hrs prior to their procedure, which will be confirmed prior to data collection on the day of 
procedure, as this would necessitate exclusion from study. 
 
c. Study interventions and data collection 
The study staff will transport the blinded medications from the research pharmacy to the IVF 
suite on the day of the procedure. Anesthesia will log medications in EPIC per research 
pharmacy protocols. 
 
Group 1: In the pre-op suite, these patients will receive 1000mg IV acetaminophen and PO 
placebo, followed by standard protocol anesthesia and pain control as needed. 
 
Group 2: In the pre-op suite, these patients will receive 1000mg PO acetaminophen and IV 
placebo, followed by standard protocol anesthesia and pain control as needed. 
 
Group 3: 
In the pre-op suite, these patients will receive PO and IV placebo, followed by standard protocol 
anesthesia and pain control as needed. 
 
In all groups, pain control will be provided by anesthesia peri-operatively as needed. Pain 
medication such as opiates may be given post-operatively as needed for pain measured by VAS 
score. In order to be consistent in assessment of immediate post-operative pain, narcotic use, and 


 
 
5 
discharge timing per our primary outcomes, NSAIDs will be avoided in the recovery room for all 
study patients, regardless of embryo transfer timing, as they are routinely contraindicated in our 
practice for any patient undergoing a fresh embryo transfer. However, patients not undergoing 
fresh transfer may take NSAIDs at home post-operatively as needed per standard of care. 
 
The PACU nurses will assess and document VAS numeric pain scores as they do routinely in 
EPIC as well as on the study data collection sheet for the study patients. Data collection sheets 
will be secured in a lock box until input into Redcap by study staff. Study staff will review the 
data collection and study protocols with the PACU nurses prior to the start of patient enrollment. 
 
After same-day discharge from the PACU, patients will receive a call from a trained member of 
the study staff on POD2 to assess their recovery and pain medication use. The POD2 phone visit 
data collection form will be completed at this time. Ability to use NSAIDs in the non-transfer 
subgroup will be taken into account at the time of the statistical analysis. 
 
The anesthesia and IVF providers will retain the discretion to exclude patients on the day of the 
procedure from the study if they took extra analgesics in the 24 hours prior to the procedure or 
experience any non-study related complications of anesthesia and/or surgery. 
d. Current standard of care 
Current standard of care for patients undergoing oocyte retrieval involves monitored MAC 
anesthesia with opiates for pain control. 
e. Risks 
Risks to the patients will be minimized because they will be undergoing anesthesia that is the 
current standard of care, and pain will be treated, as the patient requires. The patients’ IVF cycle 
management and oocyte retrieval approach will not be altered in any way by participation in the 
study. 
An adverse reaction to acetaminophen could occur. Hepatotoxicity is possible but unlikely in the 
setting of one dose of IV acetaminophen. 
f. Equitable selection of patients  
All patients presenting for oocyte retrieval≥ 18 years old who speak English and do not possess 
any other exclusion criteria may be eligible for inclusion. Our exclusion criteria are relatively 
few and do not impair our ability to make conclusions that may benefit these patients. 
People who do not speak English will be excluded from this study due to the low volume of 
these patients in our clinic population and the inconsistent ability to arrange for appropriate 
interpreters during all study-associated interactions in the cycle. 
 
V. BIOSTATISTICAL ANALYSIS 
 
a. Specific data variables being collected for the study (e.g., data collection sheets). 
 


 
 
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Clinical data regarding pain levels, pain medication use, and time to discharge will be collected 
on a PACU data collection sheet and POD2 phone visit data collection sheet. The EPIC record 
will be used to record clinical and IVF cycle history, perioperative care, embryology findings, 
and pregnancy outcomes. 
 
b. Study endpoints. 
 
The primary study endpoints will include post-operative pain levels in PACU and after discharge 
through POD2, post-operative pain medication requirements and timing in PACU and through 
POD2, and time to discharge from PACU. Secondary endpoints include procedure length, post-
operative nausea, embryology outcomes, and pregnancy outcomes. 
 
c. Statistical methods.  
The difference in pain scores will be assessed by using Fisher’s Exact and chi-square tests as 
appropriate. A multivariable regression model will be performed to control for potentially 
confounding variables, such as maternal age, BMI, medical comorbidities, procedure duration, 
and oocytes retrieved. 
 
d. Power analysis (e.g., how sample size determined, evaluable subjects, etc.)  
 
We plan to enroll 58 patients in each of the three treatment groups (n = 174). Allowing for 
attrition of 5 patients per group (approximately 10%), we assume that we will be able to evaluate 
outcome data for 159 patients. Based on OR times from 13 patients, we estimate a mean 
recovery time of 88 minutes, with a standard deviation (SD) of 19 minutes.  Using this SD, we 
anticipate 80% power to detect a difference in mean recovery time between either of the two 
treatment groups and the standard of care of 8 minutes or greater in absolute value, or 
approximately 10%, based on two-sample t-tests at the 0.025 two-tailed significance level, where 
this significance level reflects adjustment for the two comparisons with the control group.  
 
From these 13 patients, we also estimated the SD of the VAS post-operative pain rating to be 
approximately 2.8. Using this SD, we anticipate 80% power to detect a difference in mean post-
operative pain between either of the two treatment groups and the standard of care of 1.7 or 
greater in absolute value, based on two-sample t-tests as above. Alternatively, assuming that the 
population mean pain scores for the three groups are 1, 1.5 and 2.5, respectively, then we will 
have 80% power to detect that the three group means are different, based on a one-way ANOVA 
at the 0.05 two-tailed significance level. 
 
VI. RISKS AND DISCOMFORTS (STRATIFY BY COMMON AND UNCOMMON) 
 
Drug side effects and toxicities 
Potential side effects of acetaminophen include nausea, headache, loss of appetite, rash, and 
itching. However, acetaminophen is generally very well tolerated. All other medications 
proposed for this study are currently standard of care for perioperative analgesia. 
 
Serious: 
Acetaminophen: anaphylaxis, hepatotoxicity 


 
 
7 
 
Risk to privacy: 
The collection and processing of personal data from subjects enrolled in this study will be 
limited to data that are necessary to investigate the efficacy of the study treatment protocol. The 
treatment plans and medications will be blinded by the MGH Research Pharmacy, and the 
randomization key will be maintained securely per pharmacy protocols. Study members whose 
responsibilities require access to personal data agree to keep the identity of the study subjects 
confidential. The subject’s information will be kept confidential according to HIPAA guidelines. 
Psychosocial (non-medical) risks 
Because the treatment plan involves standard care for egg retrievals with immediate management 
of pain with medications as needed, we estimate no psychosocial risks. 
 
VII. POTENTIAL BENEFITS 
 
a. Potential benefits to participating individuals. 
- Improved analgesia postoperatively 
- Decreased overall consumption of opiates postoperatively which may reduce opiate related 
complications such as postoperative nausea and vomiting 
- Decreased time to discharge from the PACU 
 
b. Potential benefits to society (e.g., increased understanding of disease process, etc.) 
Investigating the use of non-opiate alternatives for perioperative anesthesia is a crucial aspect of 
reducing the overall use of opiates in the outpatient setting and preventing new opiate addiction. 
IV acetaminophen has the potential to be a versatile and worthwhile addition to achieving 
adequate postoperative analgesia in patients undergoing a wide variety of outpatient surgical 
procedures. This research will help establish whether PO and IV acetaminophen are cost-
effective adjuncts for multimodal analgesia during oocyte retrievals. 
 
VIII. MONITORING AND QUALITY ASSURANCE 
 
a. Independent monitoring of source data 
Data will be collected by study staff from the Department of Reproductive Endocrinology and 
Infertility. Eligible patients will be logged in a secure data form on a Partner’s password-
protected computer accessible only to study staff. Data collection sheets will be stored securely 
in a lock box on Yawkey 10 during study recruitment and then entered into RedCap, a secure 
online database program, with de-identified patient ID numbers assigned. Only the PI and 
research team will have access to the online and hard copy database, and identifying information 
will not be released. After the first subject has been enrolled, the data collection binder will be 
reviewed monthly by a member of the study staff and the PI at a research meeting in a de-
identified manner. The PI will be responsible for determining whether the research should be 
altered or stopped. 
 
b. Safety monitoring (e.g. Data Safety Monitoring Board, etc.) 
The PI will evaluate all acute safety data. If 3 subjects experience a grade 2 or greater Adverse 
Event (AE) that is possibly related to study procedures, the study will be paused to fully evaluate 


 
 
8 
the safety of continuing enrollment. The PI will be responsible for reviewing the data and 
determining whether the research should be altered, paused, or stopped. Any adverse events and/ 
or decision to stop enrollment will be reported to the IRB. 
 
c. Outcomes monitoring 
The research assistant and IVF fellows will collect and monitor the data collection forms and 
Redcap database monthly for accuracy and completeness. The PI will also conduct periodic 
review of the case report forms and source documentation. The study staff will meet after 50% 
desired enrollment to review data on enrolled subjects, CRFs, and source documentation. 
 
d. Adverse event reporting guidelines. 
Throughout the duration of the study, the PI will perform ongoing evaluation of subject safety 
data in order to identify AEs and trends as soon as possible. Any unanticipated problems, 
involving risks to subjects or others including AEs, will be reported to the IRB in accordance 
with PHRC unanticipated problems reporting guidelines. 
 
IX. References 
 
1. 
Smith HA. Perioperative intravenous acetaminophen and NSAIDs. Pain Medicine. 
2011;12:961-981. 
2. 
Pergolizzi JV, Jr., Raffa RB, Tallarida R, Taylor R, Labhsetwar SA. Continuous 
multimechanistic postoperative analgesia: a rationale for transitioning from intravenous 
acetaminophen and opioids to oral formulations. Pain practice : the official journal of 
World Institute of Pain. Feb 2012;12(2):159-173. 
3. 
Memis D, Inal MT, Kavalci G, Sezer A, Sut N. Intravenous paracetamol reduced the use 
of opioids, extubation time, and opioid-related adverse effects after major surgery in 
intensive care unit. Journal of critical care. Sep 2010;25(3):458-462. 
4. 
Hartford LB, Van Koughnett JAM, Murphy PB, et al. Standardization of outpatient 
procedure (STOP) narcotics: a prospective non-inferiority study to reduce opioid use in 
outpatient general surgical procedures. J Am Coll Surg. 2018:S1072-7515(1018)32038-
32036. 
5. 
Singla NK, Parulan C, Samson R, et al. Plasma and cerebrospinal fluid pharmacokinetic 
parameters after single-dose administration of intravenous, oral, or rectal acetaminophen. 
Pain practice : the official journal of World Institute of Pain. Sep 2012;12(7):523-532. 
6. 
Dart RC, Rumack BH. Intravenous acetaminophen in the United States: iatrogenic dosing 
errors. Pediatrics. 2012;129(2):349-353. 
7. 
Macario A, Royal MA. A literature review of randomized clinical trials of intravenous 
acetaminophen (paracetamol) for acute postoperative pain. Pain practice : the official 
journal of World Institute of Pain. May-Jun 2011;11(3):290-296. 
8. 
Sinatra RS, Jahr JS, Reynolds L, et al. Intravenous acetaminophen for pain after major 
orthopedic surgery: an expanded analysis. Pain practice : the official journal of World 
Institute of Pain. Jun 2012;12(5):357-365. 
9. 
Khalili G, Janghorbani M, Saryazdi H, Emaminejad A. Effect of preemptive and 
preventive acetaminophen on postoperative pain score: a randomized, double-blind trial 
of patients undergoing lower extremity surgery. Journal of clinical anesthesia. May 
2013;25(3):188-192. 


 
 
9 
10. 
McNicol ED, Ferguson MC, Haroutounian S, Carr DB, Schumann R. Single dose 
intravenous paracetamol or intravenous propacetamol for postoperative pain. The 
Cochrane database of systematic reviews. May 23 2016(5):CD007126. 
11. 
Pasero C, Stannard D. The role of intravenous acetaminophen in acute pain management: 
a case-illustrated review. Pain Manag Nurs. 2012;13(2):107-124. 
12. 
El Chaar M, Stoltzfus J, Claros L, Wasylik T. IV Acetaminophen Results in Lower 
Hospital Costs and Emergency Room Visits Following Bariatric Surgery: a Double-
Blind, Prospective, Randomized Trial in a Single Accredited Bariatric Center. Journal of 
gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary 
Tract. Apr 2016;20(4):715-724. 
13. 
Wright TE. Opioid prescribing after oocyte-retrieval: a time for caution. Fertility and 
sterility. Oct 2018;110(5):852. 
14. 
Bortoletto P, Prabhu M, Garry EM, Huybrechts KF, Anchan RM, Bateman BT. Opioid 
dispensing patterns after oocyte retrieval. Fertility and sterility. 2018;110(5):905-909. 
 

ICF_001.pdf: 
Partners HealthCare System 
Research Consent Form 
 
 
 
General Consent Form Template 
Version Date:  January 2019 
 
 
 
Page 1 of 12 
 
Subject Identification 
Protocol Title: Assessing efficacy of IV acetaminophen for perioperative pain 
control for oocyte retrieval: a randomized, double blind, placebo-
controlled trial 
 
Principal Investigator: John C. Petrozza, MD  
 
Site Principal Investigator:       
 
Description of Subject Population: Adult patients undergoing oocyte retrievals 
under concious sedation 
 
About this consent form 
 
Please read this form carefully.  It tells you important information about a research study.  A 
member of our research team will also talk to you about taking part in this research study.  
People who agree to take part in research studies are called “subjects.”  This term will be used 
throughout this consent form. 
 
Partners HealthCare System is made up of Partners hospitals, health care providers, and 
researchers.  In the rest of this consent form, we refer to the Partners system simply as 
“Partners.” 
 
If you decide to take part in this research study, you must sign this form to show that you want to 
take part.  We will give you a signed copy of this form to keep. 
 
Key Information 
 
Taking part in this research study is up to you.  You can decide not to take part.  If you decide to 
take part now, you can change your mind and drop out later.  Your decision won’t change the 
medical care you get within Partners now or in the future.   
 
The following key information is to help you decide whether or not to take part in this research 
study.  We have included more details about the research in the Detailed Information section that 
follows the key information. 
 
Why is this research study being done? 
 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Consent Form Template 
Version Date:  January 2019 
 
 
 
 
Page 2 of 12 
 
Subject Identification 
In this research study we want to learn more about how effective acetaminophen (Tylenol) is at 
reducing pain and the time in the recovery room after oocyte (egg) retrieval. We will compare 
three types of pre-operative medications: intravenous (IV) acetaminophen, oral (PO) 
acetaminophen, and placebo (no medication), which is the current typical care. The standard 
anesthesia care will be provided afterwards. We also want to find out whether pre-operative 
acetaminophen can reduce a person’s need for opioid pain medications (such as morphine) to 
“rescue” breakthrough pain. 
How long will you take part in this research study? 
 
You will take part in this research study on the day of your oocyte retrieval. We will also call 
you for a brief follow-up phone call two days after you are discharged home. No additional 
office visits will be required. 
A member of our study staff will review your medical record to collect data regarding your 
demographic, clinical, IVF cycle, and pregnancy information, which will be kept confidential for 
your privacy. This may occur up to one year after your procedure. You do not need to do 
anything for this part of the study. 
 
What will happen if you take part in this research study? 
 
If you decide to join this research study, the following things will happen:  
 
You must agree to avoid pain medications during the 24 hours prior to your egg retrieval.  
 
We will then assign you by chance (like a coin toss) to one of three study groups for pre-
operative (prior to egg retrieval) medication: 
-IV acetaminophen plus oral placebo (pill without medicine) 
-IV placebo (liquid without medicine) plus oral acetaminophen 
-IV placebo plus oral placebo 
After being given one of the three above sets of medications, standard anesthesia will be 
administered during the procedure, and any pain will be treated. You, your nurse, the study staff, 
and your primary fertility physician will not know which study group you are in. The 
anesthesiologist providing you with anesthesia during your procedure will know the study group 
you are in to make sure he or she can safely provide you anesthesia care.  
 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Consent Form Template 
Version Date:  January 2019 
 
 
 
 
Page 3 of 12 
 
Subject Identification 
Why might you choose to take part in this study? 
 
We cannot promise any benefits to you from taking part in this research study.  However, 
possible benefits may include reduced pain after surgery, reduced need for opioid medication, 
and shorter time to discharge after your retrieval.  Other women undergoing egg retrievals may 
benefit in the future from what we learn in this study. 
 
Why might you choose NOT to take part in this study? 
 
Taking part in this research study has some risks and requirements that you should consider 
carefully. Important risks and possible discomforts to know about include primarily side effects 
from acetaminophen use. 
 
A detailed description of side effects, risks, and possible discomforts can be found later in this 
consent form in the section called “What are the risks and possible discomforts from being in this 
research study?” 
 
What other treatments or procedures are available for your condition? 
 
Other available treatments or procedures that are available for post-operative pain management 
include IV or oral opioids and NSAIDs. Any post-operative pain will be treated appropriately 
regardless of participation in the study.
 
If you have questions or concerns about this research study, whom can 
you call? 
 
You can call us with your questions or concerns.  Our telephone numbers are listed below.  Ask 
questions as often as you want.   
 
John C. Petrozza M.D. is the person in charge of this research study.  You can call him at 617-
726-8868, available M-F 9-5. You can also contact Jingping Wang M.D., Ph.D. at 617-726-
2000 M-F 9-5 with questions about this research study. 
 
If you have questions about the scheduling of appointments or study visits, call Dr. Petrozza at 
617-726-8868.
 
If you want to speak with someone not directly involved in this research study, please contact 
the Partners Human Research Committee office.  You can call them at 857-282-1900. 
 
You can talk to them about: 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Consent Form Template 
Version Date:  January 2019 
 
 
 
 
Page 4 of 12 
 
Subject Identification 
▪ Your rights as a research subject 
▪ Your concerns about the research 
▪ A complaint about the research 
▪ Any pressure to take part in, or to continue in the research study 
 
Detailed Information 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law.  This Web site will not include information that can identify you.  At most, the 
Web site will include a summary of the results.  You can search this Web site at any time. 
 
Why is this research study being done? 
 
In this research study we want to learn more about how effective certain medications are at 
reducing pain after oocyte (egg) retrieval surgery and how effective they are at reducing the time 
between the retrieval and discharge from the hospital.  We will compare three types of pre-
operative medications: intravenous (IV) acetaminophen, oral (PO) acetaminophen, and placebo 
(no medication), which is the current typical care. The placebo looks exactly like the 
acetaminophen, but contains no acetaminophen. Placebos are used in research studies to see if 
the results are due to the study drug or due to other reasons. 
The standard anesthesia care will be provided afterwards. We also want to find out whether IV 
acetaminophen can reduce a person’s need for opioid pain medications (such as morphine) to 
“rescue” breakthrough pain. 
Both forms of acetaminophen are currently approved by the U.S. Food and Drug Administration 
(FDA) for the treatment of pain.  
You have been asked to take part in this study because you are scheduled to have oocyte (egg) 
retrieval. This study will have three research groups.  Each group of the study will have 
approximately 58 subjects. About 174 people will take part in this research study, all at the 
Massachusetts General Hospital (MGH) 
 
The New England Fertility Society is funding this study. 
 
Who will take part in this research? 
 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Consent Form Template 
Version Date:  January 2019 
 
 
 
 
Page 5 of 12 
 
Subject Identification 
We are asking you to take part in this rsearch study because you are over age 18 and planning to 
undergo an egg retrieval as a part of your fertility treatment. Approximately 174 patients will 
participate in this study at MGH. The New England Fertility Society is providing funding for this 
study.  
 
What will happen in this research study? 
 
If you decide to join this research study, the following things will happen: 
 
Prior to Egg Retrieval 
You must agree to avoid pain medications like Tylenol or ibuprofen in the 24 hours prior to your 
procedure.  
 
Day of Egg Retrieval 
An MGH Research Pharmacist will then randomly assign you to one of three study groups for 
pre-operative (prior to egg retrieval) medication: 
-IV acetaminophen plus oral placebo (pill without medicine) 
-IV placebo (liquid without medicine) plus oral acetaminophen 
-IV placebo plus oral placebo 
You will have a 1 in 3 chance of being assigned to each of the 3 study groups. You and the study 
doctor cannot choose your study group. The medications are prepared by the MGH Research 
Pharmacy. 
 
After signing an informed consent with the IVF docter, you will be given one of the three above 
sets of medications before your egg retrieval in the pre-operative suite. Next, standard anesthesia 
will be administered during the procedure, and any pain will be treated. Your nurse will record 
what pain medications you require in the recovery room and how much pain you are in. 
 
You, your nurse, the study staff, and your primary fertility physician will not know which study 
group you are in. The anesthesiologist providing you with anesthesia during your procedure will 
know the study group you are in to make sure he or she can safely provide you anesthesia care.  
 
A notation that you are taking part in this research study may be made in your medical record.  
Information from the research that relates to your general medical care may be included in the 
record (for example, list of allergies, results of standard blood tests done at the hospital labs). 
 
After Egg Retrieval 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Consent Form Template 
Version Date:  January 2019 
 
 
 
 
Page 6 of 12 
 
Subject Identification 
You will receive a phone call two days after your egg retrieval to ask you about your recovery 
and any pain medication used at home. This is the last participation from you for the study. 
 
A member of our study staff will also review your medical record to collect data regarding your 
demographic, non identifying information, as well as your cycle and pregnancy outcomes. This 
will occur at three instances, occuring at one month, three months, and one year  occur up to one 
year after your procedure. 
 
Stopping the Study Early 
If you decide to stop taking part in the study for any reason, you may do so at any time. 
The study doctor may also take you out of the study without your permission.  
This may happen because: 
- 
Acetaminophen or other pain medication was used in the 24 hours prior to surgery. 
- 
In the unlikely event that you are unable to participate in the study due to unexpected 
events such as requiring intubation, surgery, transfusion, or intensive care after your 
procedure.
 
How may we use and share your samples and health information for other 
research?
 
Your health information collected for this study will NOT be used or shared for other research, 
even if we remove identifiable information like your name, medical record number, or date of 
birth. 
 
Will you get the results of this research study? 
 
No.  The research study we are doing is only a stepping stone in understanding pain management 
during and after egg retrieval. Therefore, no information about the results of this research study 
or the results of your individual participation in the research study will be given to you or your 
doctor.  
 
What are the risks and possible discomforts from being in this research 
study? 
 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Consent Form Template 
Version Date:  January 2019 
 
 
 
 
Page 7 of 12 
 
Subject Identification 
Important risks and possible discomforts to know about include primarily side effects from 
acetaminophen use. Any postoperative pain will be treated regardless of study participation or 
group. 
 
Risks of IV and Oral Acetaminophen (Tylenol) 
- 
This study medication contains acetaminophen. It is not safe to take more than 4 
grams (4,000 milligrams) total of acetaminophen in one day. For Tylenol® Extra 
Strength, it is not safe to take more than 3 grams (3,000 milligrams) in one day.  In 
this study, only 1 gram of acetaminophen will be given. 
- 
Other risks include: nausea, vomiting, headache, and insomnia (inability to sleep) in 
adult patients 
- 
Some of the rare, but serious risks include: anaphylaxis (allergic reaction) or 
hepatotoxicity (liver damage) 
 
Call your doctor right away or seek urgent medical attention if you notice any of 
these side effects post-operatively: 
- 
Rash, swelling in face, difficulty breathing, or any other concerns for allergic reaction 
- 
Blistering, peeling, or red skin rash (IV form) 
- 
Pain, itching, burning, swelling, or a lump under your skin where the needle was 
placed (IV form) 
- 
Dark urine or pale stools, nausea, vomiting, loss of appetite, severe stomach pain, 
yellow skin or eyes 
- 
Pain that lasts longer than 5 days 
 
Risks of loss of Confidentiality 
Despite multiple methods to protect patient privacy, breaches in confidentiality are possible. We 
will have several procedures in place to minimize this. 
Unknown Risks 
There may be other risks that are currently unknown. 
What are the possible benefits from being in this research study? 
 
We cannot promise any benefits to you from taking part in this research study.  However, 
possible benefits may include reduced pain after surgery, reduced need for opioid medication, 
and shorter time to discharge after your retrieval. Other women undergoing egg retrievals may 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Consent Form Template 
Version Date:  January 2019 
 
 
 
 
Page 8 of 12 
 
Subject Identification 
benefit in the future from what we learn in this study because we may be able to effectively treat 
their pain with reduced amounts of opioids and discharge them sooner from the recovery room. 
 
What other treatments or procedures are available for your condition? 
 
Any pain that you experience during or after your egg retrieval procedure will be treated as 
appropriate. Other treatments for perioperative pain include: IV or PO opioids (fentanyl, 
morphine, oxycodone, hydromorphone). NSAIDs such as motrin or toradol are also sometimes 
used for pain control in patients who are not planning to undergo fresh embryo transfer. 
However, NSAIDs will not be used in study patients post-operatively in the recovery room in 
order to consistently assess the impact of pre-operative acetaminophen in all study patients 
regardless of transfer timing. Usual standard of care for management of post-operative pain at 
home with Tylenol (transfer patients) or Tylenol and NSAIDs (non-transfer patients) will still 
apply.
 
Can you still get medical care within Partners if you don’t take part in 
this research study, or if you stop taking part?  
 
Yes.  Your decision won’t change the medical care you get within Partners now or in the future.  
There will be no penalty, and you won’t lose any benefits you receive now or have a right to 
receive.  
 
We will tell you if we learn new information that could make you change your mind about taking 
part in this research study. 
 
 
What should you do if you want to stop taking part in the study? 
 
If you take part in this research study, and want to drop out, you should tell us.  We will make 
sure that you stop the study safely.  We will also talk to you about follow-up care, if needed. 
 
Also, it is possible that we will have to ask you to drop out of the study before you finish it.  If 
this happens, we will tell you why.  We will also help arrange other care for you, if needed.  
 
 
Will you be paid to take part in this research study? 
 
You will not be paid for taking part in this research study. 
 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Consent Form Template 
Version Date:  January 2019 
 
 
 
 
Page 9 of 12 
 
Subject Identification 
What will you have to pay for if you take part in this research study? 
 
Study funds will pay for certain study-related items and services.  We may bill your health 
insurer for, among other things, routine items and services you would have received even if you 
did not take part in the research.  You will be responsible for payment of any deductibles and co-
payments required by your insurer for this routine care or other billed care.  If you have any 
questions about costs to you that may result from taking part in the research, please speak with 
the study doctors and study staff.  If necessary, we will arrange for you to speak with someone in 
Patient Financial Services about these costs.
 
What happens if you are injured as a result of taking part in this 
research study?
 
We will offer you the care needed to treat any injury that directly results from taking part in this 
research study.  We reserve the right to bill your insurance company or other third parties, if 
appropriate, for the care you get for the injury.  We will try to have these costs paid for, but you 
may be responsible for some of them.  For example, if the care is billed to your insurer, you will 
be responsible for payment of any deductibles and co-payments required by your insurer. 
 
Injuries sometimes happen in research even when no one is at fault.  There are no plans to pay 
you or give you other compensation for an injury, should one occur.  However, you are not 
giving up any of your legal rights by signing this form. 
 
If you think you have been injured or have experienced a medical problem as a result of taking 
part in this research study, tell the person in charge of this study as soon as possible.  The 
researcher's name and phone number are listed in the beginning of this consent form.
 
 
If you take part in this research study, how will we protect your privacy? 
 
Federal law requires Partners to protect the privacy of health information and related information 
that identifies you.  We refer to this information as “identifiable information.” 
 
In this study, we may collect identifiable information about you from: 
• Past, present, and future medical records 
• Research procedures, including research office visits, tests, interviews, and 
questionnaires 
 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Consent Form Template 
Version Date:  January 2019 
 
 
 
 
Page 10 of 12 
 
Subject Identification 
Who may see, use, and share your identifiable information and why they may need 
to do so: 
• Partners researchers and staff involved in this study 
• The sponsor(s) of the study, and people or groups it hires to help perform this research or 
to audit the research 
• Other researchers and medical centers that are part of this study 
• The Partners ethics board or an ethics board outside Partners that oversees the research 
• A group that oversees the data (study information) and safety of this study 
• Non-research staff within Partners who need identifiable information to do their jobs, 
such as for treatment, payment (billing), or hospital operations (such as assessing the 
quality of care or research) 
• People or groups that we hire to do certain work for us, such as data storage companies, 
accreditors, insurers, and lawyers 
• Federal agencies (such as the U.S. Department of Health and Human Services (DHHS) 
and agencies within DHHS like the Food and Drug Administration, the National 
Institutes of Health, and the Office for Human Research Protections), state agencies, and 
foreign government bodies that oversee, evaluate, and audit research, which may include 
inspection of your records 
• Public health and safety authorities, if we learn information that could mean harm to you 
or others (such as to make required reports about communicable diseases or about child 
or elder abuse) 
• Other:  N/A 
 
Some people or groups who get your identifiable information might not have to follow the same 
privacy rules that we follow and might use or share your identifiable information without your 
permission in ways that are not described in this form.  For example, we understand that the 
sponsor of this study may use your identifiable information to perform additional research on 
various products or conditions, to obtain regulatory approval of its products, to propose new 
products, and to oversee and improve its products’ performance.  We share your identifiable 
information only when we must, and we ask anyone who receives it from us to take measures to 
protect your privacy.  The sponsor has agreed that it will not contact you without your 
permission and will not use or share your identifiable information for any mailing or marketing 
list.  However, once your identifiable information is shared outside Partners, we cannot control 
all the ways that others use or share it and cannot promise that it will remain private. 
 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Consent Form Template 
Version Date:  January 2019 
 
 
 
 
Page 11 of 12 
 
Subject Identification 
Because research is an ongoing process, we cannot give you an exact date when we will either 
destroy or stop using or sharing your identifiable information.  Your permission to use and share 
your identifiable information does not expire. 
 
The results of this research study may be published in a medical book or journal, or used to teach 
others.  However, your name or other identifiable information will not be used for these 
purposes without your specific permission. 
 
Your Privacy Rights 
 
You have the right not to sign this form that allows us to use and share your identifiable 
information for research; however, if you don’t sign it, you can’t take part in this research study. 
 
You have the right to withdraw your permission for us to use or share your identifiable 
information for this research study.  If you want to withdraw your permission, you must notify 
the person in charge of this research study in writing.  Once permission is withdrawn, you cannot 
continue to take part in the study. 
 
If you withdraw your permission, we will not be able to take back information that has already 
been used or shared with others, and such information may continue to be used for certain 
purposes, such as to comply with the law or maintain the reliability of the study. 
 
You have the right to see and get a copy of your identifiable information that is used or shared 
for treatment or for payment.  To ask for this information, please contact the person in charge of 
this research study.  You may only get such information after the research is finished.  
 
 
Informed Consent and Authorization 
 
Statement of Person Giving Informed Consent and Authorization 
 
▪ I have read this consent form. 
▪ This research study has been explained to me, including risks and possible benefits (if 
any), other possible treatments or procedures, and other important things about the study. 
▪ I have had the opportunity to ask questions. 
▪ I understand the information given to me. 
 
Signature of Subject: 
 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Consent Form Template 
Version Date:  January 2019 
 
 
 
 
Page 12 of 12 
 
Subject Identification 
I give my consent to take part in this research study and agree to allow my health information to 
be used and shared as described above. 
 
 
 
 
 
 
 
 
Subject 
Date 
Time (optional) 
 
Signature of Study Doctor or Person Obtaining Consent: 
 
Statement of Study Doctor or Person Obtaining Consent 
 
▪ I have explained the research to the study subject. 
▪ I have answered all questions about this research study to the best of my ability. 
 
 
 
 
 
 
 
 
Study Doctor or Person Obtaining Consent 
Date 
Time (optional) 
 
 
Consent Form Version:  1 
Consent Form Date: 7-31-2019