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

100 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to see if the investigators can obtain non-inferior clinical outcomes (similar numbers of oocytes) using the Cardinal protocol, a cost-conscious, low-intensity egg freezing protocol, compared to other routinely used high-intensity clinic protocols. This is a new program for Stanford's Fertility Clinic, so the investigators are assessing patient experience and cost-benefit of a low-cost, low-intensity approach that has demonstrated non-inferiority in IVF for infertility treatment, but has not been similarly evaluated in egg freezing. All enrolled participants will choose the Cardinal protocol or the routine high-intensity protocol designated by their physician. The investigators will then assess number of eggs retrieved, as well as patient satisfaction, cost, and time needed off work to complete the egg freezing cycle. The study's findings could ultimately open the door to implementation of lower-cost standardized protocols that would be more affordable and accessible to people who may otherwise not be able to pursue fertility preservation.

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 data supports the idea that Low vs High-Intensity Egg Freezing for Infertility is an effective treatment?

The available research shows that both slow freezing and vitrification methods for egg freezing have been successful, with a comparable number of healthy babies being born using either method. In one study, the survival, fertilization, pregnancy, and implantation rates were higher with vitrification compared to slow freezing. This suggests that egg freezing, whether low or high-intensity, is an effective treatment for infertility. Additionally, oocyte freezing has started to compete with embryo cryopreservation in terms of efficiency, with cumulative pregnancy rates approaching 50%, indicating its effectiveness as a treatment option. ^{1 2 3 4 5}

What data supports the effectiveness of the High-Intensity Egg Freezing Protocol treatment for infertility?

Research shows that both slow freezing and vitrification methods for egg freezing have been successful, with a comparable number of healthy babies born using either method. Vitrification, a rapid freezing technique, has shown higher survival and fertilization rates compared to slow freezing, suggesting it may be more effective for preserving eggs. ^{1 2 3 4 5}

What safety data exists for egg freezing treatments?

Egg freezing, also known as oocyte cryopreservation, is no longer considered experimental and is increasingly popular for fertility preservation. The current method of choice is vitrification due to its effectiveness. While reproductive outcomes following egg freezing are promising, there is a lack of data on long-term safety outcomes, which raises safety concerns. The procedure also involves health risks, as well as financial and psychological factors. ^{6 7 8 9 10}

Is egg freezing generally safe for humans?

Egg freezing is not considered experimental anymore and is popular among women for preserving fertility. However, while the technology is advancing and outcomes are promising, there is a lack of data on long-term safety, which raises some concerns. ^{6 7 8 9 10}

Is High-Intensity Egg Freezing Protocol a promising treatment for infertility?

Yes, High-Intensity Egg Freezing Protocol is a promising treatment for infertility. It uses a method called vitrification, which is currently the preferred way to freeze eggs because it is effective. This method has shown good results in terms of egg survival and pregnancy rates, making it a valuable option for women who want to preserve their fertility. ^{1 5 8 11 12}

How does the Low vs High-Intensity Egg Freezing treatment differ from other treatments for infertility?

The Low vs High-Intensity Egg Freezing treatment is unique because it compares two different protocols for freezing eggs: a high-intensity and a low-intensity approach. This study aims to determine which method is more effective, as current egg freezing techniques like vitrification are effective but can be cumbersome and costly. ^{1 5 8 11 12}

Research Team

Ruth Lathi, MD

Principal Investigator

Stanford University

Eligibility Criteria

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

BMI > 45

I have no medical reasons preventing me from undergoing ovarian stimulation or egg retrieval under anesthesia.

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Cryopreservation of mature and immature oocytes. [2010]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Efficiency of human oocyte slow freezing: results from five assisted reproduction centres. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Clinical efficiency of oocyte and embryo cryopreservation. [2022]

4. Japan pubmed.ncbi.nlm.nih.gov

Long-term outcomes of freeze-all strategy: A retrospective analysis from a single ART center in Japan. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Human oocyte cryopreservation: comparison between slow and ultrarapid methods. [2022]

6. Germany 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? [2022]

7. England pubmed.ncbi.nlm.nih.gov

The development and phase 1 evaluation of a Decision Aid for elective egg freezing. [2023]

8. Ireland pubmed.ncbi.nlm.nih.gov

Egg freezing and late motherhood. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Evolution of human oocyte cryopreservation: slow freezing versus vitrification. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Perinatal outcomes of singletons following vitrification versus slow-freezing of embryos: a multicenter cohort study using propensity score analysis. [2020]

11. Switzerland pubmed.ncbi.nlm.nih.gov

The Near Future of Vitrification of Oocytes and Embryos: Looking into Past Experience and Planning into the Future. [2020]

12. England pubmed.ncbi.nlm.nih.gov

Terminology associated with vitrification and other cryopreservation procedures for oocytes and embryos. [2022]