Influenza Vaccine for Infertility

(IVF-FluVac Trial)

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Center for Human Reproduction

Disqualifiers: Unfavorable endometrial, Uterine condition, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how receiving a flu shot might affect pregnancy rates in women undergoing in vitro fertilization (IVF). The study will compare two groups: one receiving the flu vaccine and another receiving a saline injection, which serves as a placebo (a harmless shot with no active ingredients). The aim is to determine if the flu shot can enhance pregnancy success through IVF. Women planning to start an IVF cycle and willing to receive a flu shot may be suitable candidates for this trial. As a Phase 4 trial, the flu vaccine is already FDA-approved and proven effective, and this research seeks to understand its benefits for more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What is the safety track record for the influenza vaccine?

Research has shown that the flu vaccine is generally safe for people. Studies have found that receiving the flu shot at the beginning of pregnancy does not increase the risk of miscarriage. In one study, the flu vaccine did not affect a woman's ability to become pregnant. Another study showed that women who received the flu shot during pregnancy did not experience more problems with their pregnancy or birth.

Most people who receive the flu shot experience only mild side effects, such as soreness at the injection site or mild reactions. The studies reviewed report no major safety issues with the vaccine. Overall, the flu vaccine is well-tolerated and does not pose serious risks. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using the influenza vaccine for infertility because it explores a completely new approach to treating this condition. Unlike traditional treatments for infertility that often involve hormonal therapies or assisted reproductive technologies, this trial investigates the potential of an immune response, triggered by a common vaccine, to play a role in fertility. This could open up a novel pathway for managing infertility, offering a simpler, less invasive option that could be more accessible to a broader population. If successful, it might redefine how we understand and treat infertility, expanding possibilities beyond the current standard methods.

What evidence suggests that the influenza vaccine might be an effective treatment for infertility?

Research has shown that the flu vaccine does not harm fertility. In a large study involving 483 pregnant individuals, 98.8% of those who received the flu shot had live births, indicating no negative effects on pregnancy. Another study found that receiving the flu vaccine did not affect the ability to conceive. This trial will compare the effects of the Influenza Vaccine with a Saline Injection placebo. This evidence suggests that the flu vaccine is likely safe and probably does not affect the success of IVF treatments. ^{2 3 5 6 7}

Who Is on the Research Team?

David H Barad, MD, MS

Principal Investigator

Director of Assisted Reproductive Technology

Norbert Gleicher, MD

Principal Investigator

Medical Director

Are You a Good Fit for This Trial?

This trial is for women planning to undergo in vitro fertilization (IVF) who are willing and able to receive an influenza vaccination. They must consent to participate in only one treatment cycle. Women with a history of poor endometrial development, contraindications for flu shots, unresolved uterine conditions affecting the womb's lining, or unwillingness to consent are excluded.

Inclusion Criteria

Signed informed consent

All women preparing to undergo an IVF cycle

You must be willing to get a flu shot.

Exclusion Criteria

I was diagnosed with a condition affecting my womb lining.

I am not willing to get a flu shot.

I have a uterine condition that affects the inside of my uterus.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment

Participants receive either influenza vaccine or saline placebo 10 days before initiating fertility treatment cycle

10 days

Treatment

Participants undergo in vitro fertilization with monitoring for clinical pregnancy and immune activation

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a second injection at the time of negative pregnancy test or clinical pregnancy

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Influenza Vaccine

Trial Overview The study aims to see if getting a flu shot affects pregnancy rates in women going through IVF. Participants will be randomly assigned either the influenza vaccine or sterile saline as a control group before starting their IVF treatment.

How Is the Trial Designed?

Group I: Influenza Vaccine Experimental Treatment 1 Intervention

O.5 mL single dose influenza vaccine suspension administered intramuscularly

Group II: Saline Injection Placebo Group 1 Intervention

O.5 ml of sterile Saline administered intramuscularly

Influenza Vaccine is already approved in United States, European Union for the following indications:

Approved in United States as Afluria for:

• Prevention of influenza A and B

Approved in European Union as Fluarix for:

• Prevention of influenza A and B

Approved in United States as Flucelvax for:

• Prevention of influenza A and B

Approved in European Union as Flulaval for:

• Prevention of influenza A and B

Approved in United States as Fluzone for:

• Prevention of influenza A and B

Approved in European Union as Fluad for:

• Prevention of influenza A and B in adults 65 years and older

Approved in United States as FluMist for:

• Prevention of influenza A and B in individuals 2-49 years old

Approved in European Union as Influvac for:

• Prevention of influenza A and B

Approved in European Union as Optaflu for:

• Prevention of influenza A and B

Approved in European Union as Vaxigrip for:

• Prevention of influenza A and B

Who Is Running the Clinical Trial?

Center for Human Reproduction

Lead Sponsor

Trials

14

Recruited

1,200+

Foundation for Human Reproduction

Collaborator

Trials

2

Recruited

360+

Published Research Related to This Trial

Fluad, an MF59-adjuvanted subunit influenza vaccine, is specifically designed to enhance immune responses in vulnerable populations, particularly the elderly, who may have weakened immune systems.

Clinical effectiveness data indicate that Fluad provides greater immunogenicity compared to conventional influenza vaccines, potentially offering better protection against the disease in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MF59-adjuvanted subunit influenza vaccine: an improved interpandemic influenza vaccine for vulnerable populations. Puig Barberà, J., González Vidal, D.[2013]

In a study of 483 pregnant individuals vaccinated with the quadrivalent inactivated influenza vaccine (IIV4) over four flu seasons, 98.8% reported live births, indicating a high safety profile for the vaccine during pregnancy.

The rates of adverse infant outcomes, such as preterm birth (7.2%), low birth weight (5.4%), and major congenital malformations (0.8%), were found to be lower than or similar to the general population, suggesting that IIV4 does not pose significant safety concerns for pregnant individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Prospective Cohort Study on Pregnancy Outcomes of Persons Immunized with a Seasonal Quadrivalent Inactivated Influenza Vaccine during Pregnancy. Robinson, C., Oberye, J., van Boxmeer, J., et al.[2023]

A comprehensive analysis of 36 trials involving 7532 adults aged 65 and older showed that the MF59-adjuvanted trivalent influenza vaccine (aIIV3) has a similar safety profile to the nonadjuvanted vaccine (IIV3), with comparable rates of adverse events (24.8% for aIIV3 vs 26.7% for IIV3).

The study found no significant differences in serious adverse events or other safety concerns between the two vaccines, indicating that aIIV3 is a safe option for older adults receiving influenza vaccination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cumulative clinical experience with MF59-adjuvanted trivalent seasonal influenza vaccine in young children and adults 65 years of age and older. Lindert, K., Leav, B., Heijnen, E., et al.[2019]

In a safety surveillance study of the Vaxigrip and Intanza 15 µg influenza vaccines during the 2016/17 season, 1.8% of Vaxigrip recipients and 2.1% of Intanza recipients reported suspected adverse reactions within 7 days, indicating a generally low incidence of side effects.

The safety profiles of both vaccines remained consistent with previous years, with no significant increase in adverse reactions, suggesting that both vaccines are safe for use in the population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Report from enhanced safety surveillance of two influenza vaccines (Vaxigrip and Intanza 15 μg) in two European countries during influenza season 2016/17 and comparison with 2015/16 season. Chabanon, AL., Bricout, H., Ballandras, C., et al.[2019]

In a safety surveillance study involving over 2,000 vaccinees during the 2015/16 influenza season, both Vaxigrip and Intanza 15 µg vaccines showed a low rate of suspected adverse reactions (ARs), with 3.2% and 3.0% reporting ARs respectively, consistent with their known safety profiles.

The study confirmed that there were no significant changes in reactogenicity for either vaccine, indicating that the enhanced safety surveillance effectively monitored vaccine safety without raising new concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Passive enhanced safety surveillance for Vaxigrip and Intanza 15 µg in the United Kingdom and Finland during the northern hemisphere influenza season 2015/16. Bricout, H., Chabanon, AL., Souverain, A., et al.[2018]

The virosomal influenza vaccine (Invivac) demonstrated high efficacy, with 76 to 99% of subjects with low pre-vaccination antibody levels achieving protective immunity after vaccination, based on data from 14 clinical studies involving 2865 participants.

The vaccine was found to be safe, with acceptable rates of mild and transient local and systemic reactions, making it suitable for both healthy adults and those with chronic illnesses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Virosomal influenza vaccine: a safe and effective influenza vaccine with high efficacy in elderly and subjects with low pre-vaccination antibody titers. de Bruijn, IA., Nauta, J., Gerez, L., et al.[2005]

In a clinical trial involving 2640 adults aged 50 and older, Flublok showed non-inferior safety compared to AFLURIA regarding hypersensitivity reactions, with only a slight difference in reported cases (0.15%).

Both vaccines had similar reactogenicity and overall adverse event profiles, indicating that Flublok is a safe alternative for seasonal influenza vaccination in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized comparison of the safety of Flublok(®) versus licensed inactivated influenza vaccine in healthy, medically stable adults ≥ 50 years of age. Izikson, R., Leffell, DJ., Bock, SA., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7360345/

A prospective study of influenza vaccination and time to ... Conclusions: Our data indicate no adverse effect of influenza vaccination on fecundability.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02947217

Effect of Influenza Vaccination on IVF Outcomes - IVF A randomized controlled trial to evaluate the effect of influenza vaccination on clinical pregnancy rates among women undergoing in vitro fertilization.

3. asrm.org asrm.org/practice-guidance/practice-committee-documents/current-recommendations-for-vaccines-for-patients-planning-pregnancy/

Current recommendations for vaccines for patients ... In contrast, intranasal influenza vaccines contain live attenuated virus and should not be administered during pregnancy. Pregnancy should be avoided for 1 ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0264410X2030548X

A prospective study of influenza vaccination and time to ... Influenza vaccination was common (47% of females and 37% of males). Our data indicate no adverse effect of influenza vaccination on fecundability.

5. withpower.com withpower.com/trial/phase-4-infertility-2017-7b405

Influenza Vaccine for Infertility (IVF-FluVac Trial) In a study of 483 pregnant individuals vaccinated with the quadrivalent inactivated influenza vaccine (IIV4) over four flu seasons, 98.8% reported live births, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10424825/

Risk of Miscarriage in Relation to Seasonal Influenza ... Receipt of seasonal inactivated influenza vaccines around the start of pregnancy was not associated with an increased rate of miscarriage.

7. sciencedirect.com sciencedirect.com/science/article/pii/S2589537020302662

Safety and protective effects of maternal influenza ... The study showed that influenza vaccination during pregnancy is not associated with adverse pregnancy, foetal or birth outcomes.