Low vs High-Intensity Egg Freezing for Infertility

Overseen By Esther Chung, MD

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: Stanford University

Disqualifiers: Severe OHSS, Diminished ovarian reserve, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 4-6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates whether a low-intensity, cost-effective method for freezing eggs is as effective as the usual high-intensity approach. It targets individuals seeking fertility preservation, particularly those with ovaries and hormone levels indicating a healthy ovarian reserve. Participants will choose between the new low-cost protocol (Low-Intensity Egg Freezing Protocol) and the standard high-intensity protocol (High-Intensity Egg Freezing Protocol). Researchers will assess the number of eggs collected, participant satisfaction, cost, and time off work. The goal is to determine if the low-cost method can make egg freezing more affordable and accessible. As an unphased trial, this study provides a unique opportunity to advance fertility preservation accessibility and affordability.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with your doctor.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that these egg freezing protocols are safe?

Research has shown that both high-intensity and low-intensity egg freezing methods are generally safe. The high-intensity method is well-established, and most women tolerate it well. After thawing, about 74% of the eggs survive, and around 68.8% of these eggs are successfully fertilized.

The low-intensity method is newer but has demonstrated similar results in studies. It aims to be less stressful both financially and physically. Some research suggests that this method does not affect egg quality or embryo development.

Overall, both methods have been tested and appear well-tolerated, with no major safety concerns reported. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores two different approaches to egg freezing, which could offer new insights into fertility treatments. The low-intensity protocol is unique because it offers a potentially more affordable and less physically demanding option for patients. On the other hand, the high-intensity protocol serves as a benchmark, representing the current standard of care, which typically involves more rigorous hormonal stimulation. By comparing these two methods, researchers hope to find out if a less intense approach can be just as effective, providing more accessible options for individuals seeking fertility preservation.

What evidence suggests that this trial's egg freezing protocols could be effective for infertility?

This trial will compare the effectiveness of high-intensity and low-intensity egg freezing protocols. Research has shown that high-intensity egg freezing methods are effective, with 74% of eggs surviving the thawing process and a 36.4% chance of pregnancy per patient using their frozen eggs. Participants in this trial may choose the high-intensity protocol. Conversely, studies on low-intensity methods suggest similar results, showing no difference in egg quality or embryo development compared to high-intensity methods. Participants may also opt for the low-intensity protocol, which could offer similar benefits while being more affordable and accessible. Both methods aim to help women preserve their fertility for future use, but the effectiveness of the low-intensity method for egg freezing remains under study. ^{1 2 4 5 6}

Who Is on the Research Team?

Ruth Lathi, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

The Stanford Egg Freezing Study is for ovary-bearing individuals aged 18-40 who want to freeze their eggs and have an Anti-Müllerian Hormone (AMH) level between 0.3 ng/mL and 7 ng/mL. It's not suitable for those with a high risk of severe ovarian hyperstimulation syndrome (OHSS), a BMI over 45, severely low ovarian reserve, or any conditions that make egg retrieval under anesthesia unsafe.

Inclusion Criteria

AMH > 0.3 ng/mL

AMH < 7 ng/mL

Exclusion Criteria

AMH > 7 ng/mL or physician concern for risk of developing severe OHSS

Severe diminished ovarian reserve (DOR) defined as AMH < 0.3 ng/mL or FSH > 15

BMI > 45

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo the egg freezing cycle using either the low-cost, low-intensity Cardinal protocol or the high-intensity clinic protocol

4-6 weeks

Multiple visits for bloodwork and ultrasounds

Follow-up

Participants are monitored for satisfaction, cost, and time off work after the egg retrieval

1-2 months

Post-cycle survey

What Are the Treatments Tested in This Trial?

Interventions

• High-Intensity Egg Freezing Protocol
• Low-Intensity Egg Freezing Protocol

Trial Overview This study compares two egg freezing protocols: the Cardinal protocol, which is cost-effective and less intense, versus traditional high-intensity methods used in clinics. Participants will either choose the Cardinal protocol or be assigned the routine method by their physician. The number of eggs retrieved, patient satisfaction, costs involved, and time off work are evaluated.

How Is the Trial Designed?

Group I: Low-Intensity Protocol Experimental Treatment 1 Intervention

Participants choose the low-cost, low-intensity egg-freezing protocol

Group II: High-intensity protocol Active Control 1 Intervention

Participants choose a routine high-intensity egg-freezing protocol

High-Intensity Egg Freezing Protocol is already approved in United States, European Union for the following indications:

Approved in United States as Egg Freezing for:

• Fertility Preservation
• Infertility Treatment

Approved in European Union as Oocyte Cryopreservation for:

• Fertility Preservation
• Infertility Treatment

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Published Research Related to This Trial

Freezing oocytes within 2 hours of retrieval significantly improves embryo quality, with a best-quality embryo rate of 33.24% compared to 16.20% when frozen later (P < 0.001).

The pregnancy and implantation rates are also much higher for oocytes frozen within 2 hours, showing rates of 30.07% and 15.08% respectively, compared to 8.97% and 4.57% for those frozen after 2 hours (P < 0.001).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficiency of human oocyte slow freezing: results from five assisted reproduction centres. Parmegiani, L., Bertocci, F., Garello, C., et al.[2019]

The freeze-all strategy in in vitro fertilization (IVF) shows high embryo survival rates, with 99.1% for vitrified embryos and 92.5% for slow-frozen embryos, indicating its effectiveness in preserving embryos for future use.

This approach is particularly beneficial for patients aged 42 years or younger, as it results in higher pregnancy rates with frozen-thawed embryo transfers compared to fresh transfers, especially in cases where progesterone levels are elevated during oocyte retrieval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes of freeze-all strategy: A retrospective analysis from a single ART center in Japan. Asada, Y., Tokoro, M., Sonohara, M., et al.[2023]

The Decision Aid for elective egg freezing was found to be highly acceptable and useful among 26 Australian women, significantly improving their knowledge about egg freezing and reducing decisional conflict, as evidenced by a decrease in the Decisional Conflict Scale score from 65 to 7.5.

Participants reported high satisfaction with the Decision Aid, with 25 out of 26 expressing they would recommend it to others, indicating its potential as a valuable tool for women considering elective egg freezing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The development and phase 1 evaluation of a Decision Aid for elective egg freezing. Sandhu, S., Hickey, M., Lew, R., et al.[2023]

Egg freezing has evolved from a treatment for ovarian insufficiency to a widely accepted method for fertility preservation among healthy women, with vitrification being the most effective technique currently available.

While reproductive outcomes after egg freezing are promising, they are significantly affected by maternal age, and there is a lack of long-term safety data, raising concerns about potential health risks and socioeconomic factors associated with the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Egg freezing and late motherhood. Mintziori, G., Veneti, S., Kolibianakis, EM., et al.[2019]

In a study of 2216 patients, the cumulative live birth rate (CLBR) was significantly lower for those using the freeze-all strategy (50.2%) compared to those undergoing fresh embryo transfer (58.1%), indicating that fresh transfers may be more effective for achieving live births.

Patients in the freeze-all group also experienced a longer median time to pregnancy (61 days) compared to the fresh transfer group (5 days), suggesting that while freeze-all can prevent complications like ovarian hyperstimulation syndrome, it may delay conception.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does the freeze-all strategy improve the cumulative live birth rate and the time to become pregnant in IVF cycles? Johnson, S., Vandromme, J., Larbuisson, A., et al.[2022]

A study involving 3199 live-born singletons from frozen-thawed embryo transfer cycles found that embryo vitrification does not increase the risk of adverse perinatal outcomes compared to slow-freezing, with no significant differences in pre-term birth, low birth weight, or other complications.

Vitrification showed similar safety profiles to slow-freezing while also having higher embryo survival and live birth rates, suggesting it is a reliable method for embryo cryopreservation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perinatal outcomes of singletons following vitrification versus slow-freezing of embryos: a multicenter cohort study using propensity score analysis. Gu, F., Li, S., Zheng, L., et al.[2020]

Vitrification has become the preferred method for preserving oocytes and embryos at low temperatures, replacing older freezing techniques that were less effective, especially for oocytes.

Despite its advantages, vitrification is still a complex and expensive process, prompting ongoing research into improving its efficiency and reducing costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Near Future of Vitrification of Oocytes and Embryos: Looking into Past Experience and Planning into the Future. Arav, A., Natan, Y.[2020]

Both slow cooling and vitrification techniques for oocyte freezing have been shown to result in a similar number of healthy babies being born, indicating that both methods are effective.

Slow cooling is more commonly used in practice, while vitrification is primarily utilized in egg donor programs, suggesting a need for further randomized studies to determine the optimal protocol for oocyte freezing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cryopreservation of mature and immature oocytes. Borini, A., Bianchi, V.[2010]

Cumulative delivery rates in IVF can reach 50-60% for good prognosis patients when including frozen embryos, highlighting the importance of cryopreservation in assessing treatment success.

Recent advancements in oocyte cryopreservation methods have made them competitive with traditional embryo freezing, potentially changing the standard practices in IVF and improving overall pregnancy rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficiency of oocyte and embryo cryopreservation. Borini, A., Cattoli, M., Bulletti, C., et al.[2022]

Oocyte cryopreservation using vitrification is significantly more effective than slow freezing, showing higher survival, implantation, and pregnancy rates based on data from the Italian National Assisted Reproductive Technology Register covering 2009-2014.

Despite the advantages of vitrification, the success rates can vary widely among different centers, and transferring fresh or cryopreserved embryos still yields better outcomes than using embryos from cryopreserved oocytes, except in highly experienced centers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolution of human oocyte cryopreservation: slow freezing versus vitrification. Levi-Setti, PE., Patrizio, P., Scaravelli, G.[2018]

In a study involving 286 thawing cycles of oocytes, vitrification (ultrarapid cooling) showed significantly higher survival rates (78.9% vs. 57.9%) compared to slow freezing, indicating it may be a more effective method for oocyte cryopreservation.

Vitrification also resulted in better fertilization (72.8% vs. 64.6%), pregnancy (18.2% vs. 7.6%), and implantation rates (9.3% vs. 4.3%) than slow freezing, suggesting it leads to improved outcomes for women undergoing IVF for infertility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human oocyte cryopreservation: comparison between slow and ultrarapid methods. Fadini, R., Brambillasca, F., Renzini, MM., et al.[2022]

The paper provides a comprehensive overview of various cryopreservation techniques used for oocytes, embryos, sperm, and reproductive tissues, clarifying the specialized terminology associated with these procedures.

By explaining the physical, chemical, and biological processes involved in slow cooling, rapid cooling, ultrarapid cooling, and vitrification, the paper aims to enhance understanding and facilitate comparisons of different cryopreservation methods in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Terminology associated with vitrification and other cryopreservation procedures for oocytes and embryos. Shaw, JM., Jones, GM.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10342811/

Outcomes of Social Egg Freezing: A Cohort Study and ... In total, 16% of the women returned to use their frozen eggs. The mean egg thaw survival rate post egg thaw was 74%. The mean egg fertilisation ...

2. asrm.org asrm.org/practice-guidance/practice-committee-documents/evidence-based-outcomes-after-oocyte-cryopreservation-for-donor-oocyte-in-vitro-fertilization-and-planned-oocyte-cryopreservation-a-guideline-2021/

Evidence-based outcomes after oocyte cryopreservation ... A review of success rates, factors that may impact success rates, and outcomes in scenarios of planned OC and cryopreserved donor oocytes.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05842070?cond=Stanford%20Protocol&viewType=Table&rank=1

NCT05842070 | The Stanford Egg Freezing Study The high-intensity egg freezing protocol is a routinely used clinic protocol where patients are coming for frequent ultrasounds and bloodwork, as well as more ...

4. rbej.biomedcentral.com rbej.biomedcentral.com/articles/10.1186/s12958-021-00884-0

Oocyte cryopreservation review: outcomes of medical oocyte ... The clinical pregnancy rate of the 11 patients who returned to use their cryopreserved oocytes was 36.4% per patient (16.7% per transfer) with a ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1472648323008271

Storage trends, usage and disposition outcomes following ... At the time of reporting, 88 (38.1%) patients had used their frozen eggs for their own fertility treatment, 109 (47.2%) patients had eggs still in storage, 27 ( ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8740039/

Oocyte cryopreservation review: outcomes of medical ... The mean survival rate post-thaw was 74.2% (median 73.7%, range 0-100%) and the mean fertilization rate was 68.8%; these rates did not differ ...