In Vitro Maturation for Infertility

Overseen By Ye Yuan, PhD

Age: < 65

Sex: Female

Trial Phase: Academic

Sponsor: Colorado Center for Reproductive Medicine

Disqualifiers: More than 2 failed IVF cycles

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a fertility treatment called in vitro maturation (IVM) to assist women facing infertility. IVM uses fewer hormones than traditional IVF, potentially reducing costs and side effects. The study targets women with polycystic ovary syndrome (PCOS) or a strong ovarian reserve, with specific criteria for ovarian health and sperm quality. Participants receive a free IVM cycle, along with essential fertility tests and treatments. This approach may suit women ready to try a new fertility method and planning an embryo transfer soon. As an unphased trial, it provides a unique opportunity to investigate innovative fertility solutions without the constraints of traditional phase requirements.

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 in vitro maturation is safe for infertility treatment?

Research has shown that in vitro maturation (IVM) is generally safe. Studies suggest that IVM can be a good option for women at risk of ovarian hyperstimulation syndrome (OHSS), a condition associated with other fertility treatments. The safety data for IVM is reassuring, though more long-term information is needed. Overall, IVM uses fewer hormones, resulting in fewer side effects compared to traditional IVF treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial?

In Vitro Maturation (IVM) is unique because it offers a different approach to infertility treatment compared to traditional in vitro fertilization (IVF). Unlike IVF, which requires eggs to fully mature inside the ovaries before retrieval, IVM allows immature eggs to be collected and then matured in a lab. This can reduce the need for high doses of hormonal stimulation, making the process potentially safer and more comfortable for patients. Researchers are excited about IVM because it could offer a less invasive and more cost-effective option for couples struggling with infertility.

What evidence suggests that in vitro maturation is effective for infertility?

Research has shown that biphasic in vitro maturation (IVM), which participants in this trial will receive, holds promise for individuals facing infertility. Studies have found that this method helps more egg cells mature, with one study reporting a 58.4% success rate. This results in more eggs being ready for fertilization. Additionally, biphasic IVM increases the chances of normal fertilization, reaching 73.8%. Reports indicate healthy pregnancies and births following this treatment. Early data suggests that children born through this process develop normally up to 24 months. This makes biphasic IVM a hopeful option for those trying to conceive. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for women facing infertility issues, particularly those with Polycystic Ovary Syndrome (PCOS), tubal factors, or a low ovarian reserve. Healthy individuals can also apply. To qualify, participants must be seeking fertility treatment and willing to undergo in vitro maturation (IVM).

Inclusion Criteria

Intend to perform embryo transfer within 4 months after completing the IVM cycle

I agree to embryo biopsy for genetic testing.

Antral follicle count (AFC) greater than 24

Exclusion Criteria

More than 2 failed IVF cycles

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a three-day low dose stimulation followed by egg retrieval and in vitro maturation of oocytes

1 week

Multiple visits for stimulation, retrieval, and laboratory procedures

Embryo Development and Transfer

Mature oocytes are fertilized and cultured to the blastocyst stage, followed by biopsy and frozen embryo transfer

2 weeks

Visits for embryo transfer and monitoring

Follow-up

Participants are monitored for pregnancy outcomes and live birth data collection

12 months

Regular follow-up visits and patient contact

What Are the Treatments Tested in This Trial?

Interventions

• IVM

Trial Overview The study tests IVM, an alternative to IVF that uses fewer hormones to mature eggs outside the body. Qualified participants will receive a free IVM cycle at CCRM Fertility including consultation, testing, genetic screening of embryos (PGT-A), anesthesia, and some medications.

How Is the Trial Designed?

Group I: Biphasic IVM Treatment Experimental Treatment 1 Intervention

Biphasic IVM of oocytes

IVM is already approved in United States, European Union, Canada for the following indications:

Approved in United States as IVM for:

• Infertility due to polycystic ovary syndrome (PCOS)
• Infertility due to ovarian hyperstimulation syndrome (OHSS) risk
• Fertility preservation before gonadotoxic cancer treatment

Approved in European Union as IVM for:

• Infertility due to PCOS
• Infertility due to OHSS risk
• Fertility preservation before gonadotoxic cancer treatment

Approved in Canada as IVM for:

• Infertility due to PCOS
• Infertility due to OHSS risk
• Fertility preservation before gonadotoxic cancer treatment

Who Is Running the Clinical Trial?

Colorado Center for Reproductive Medicine

Lead Sponsor

Trials

7

Recruited

700+

Published Research Related to This Trial

In-vitro maturation (IVM) allows immature oocytes to mature from the germinal vesicle stage to metaphase 2 in about 28-36 hours, showing promise for patients with polycystic ovarian syndrome and normal menstruating women.

Approximately 300 healthy children have been born worldwide from IVM, indicating its potential as a safe alternative to standard ovarian stimulation, although further research is needed to fully understand its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lessons learned from introducing an in-vitro maturation programme into clinical practice. von Otte, S., Schöpper, B., Diedrich, K., et al.[2019]

In-vitro maturation (IVM) of immature oocytes, especially when combined with hormonal priming, has shown improved maturation rates and embryo quality, leading to pregnancy rates of 30-35% in women with polycystic ovaries or polycystic ovary syndrome.

Over 300 healthy infants have been born from IVM, demonstrating its efficacy as a viable alternative to traditional IVF methods, allowing for successful pregnancies without the need for ovarian stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

State of the art in in-vitro oocyte maturation. Chian, RC., Lim, JH., Tan, SL.[2019]

In a study of 531 women with polycystic ovary syndrome (PCOS), switching from in vitro fertilization (IVF) to in vitro maturation (IVM) did not significantly change cumulative live birth rates, but natural IVM showed a higher clinical pregnancy rate (36.0% vs. 26.0%).

Both natural IVM and switching to IVF/M had no cases of ovarian hyperstimulation syndrome (OHSS), indicating that these procedures are safe and effective options for managing infertility in PCOS patients with unexpected poor ovarian response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness, Flexibility and Safety of Switching IVF to IVM as a Rescue Strategy in Unexpected Poor Ovarian Response for PCOS Infertility Patients. Guo, W., Zheng, X., Zheng, D., et al.[2023]

In vitro maturation (IVM) is a modified IVF technique that allows for the collection of immature oocytes, reducing the need for gonadotrophin stimulation and minimizing the risk of ovarian hyperstimulation syndrome (OHSS), especially in high-risk patients like those with polycystic ovary syndrome (PCOS).

Recent advancements in IVM, including pre-maturation protocols and new culture media additives, have improved success rates and demonstrated safety regarding neonatal and childhood outcomes, making it a promising option for fertility preservation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro maturation. Walls, ML., Hart, RJ.[2019]

Oocyte in vitro maturation (IVM) is a well-established assisted reproductive technology that allows for the collection and maturation of immature oocytes, but its clinical use remains limited despite its non-experimental status.

This review aims to educate reproductive medicine professionals on the safe and effective application of IVM, highlighting its potential benefits for specific patient groups based on the latest evidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perspectives on the development and future of oocyte IVM in clinical practice. De Vos, M., Grynberg, M., Ho, TM., et al.[2021]

Rescue in vitro maturation (IVM) can be an effective alternative for polycystic ovarian syndrome (PCOS) patients undergoing IVF who are at risk of ovarian hyperstimulation syndrome (OHSS) or have poor responses to ovarian stimulation, as demonstrated in a study of five patients.

In the study, IVM led to successful oocyte retrieval and resulted in live births for some patients, indicating that this approach can mitigate risks associated with traditional IVF methods while still achieving positive outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rescue In Vitro Maturation in Polycystic Ovarian Syndrome Patients Undergoing In Vitro Fertilization Treatment who Overrespond or Underrespond to Ovarian Stimulation: Is It A Viable Option? A Case Series Study. Fatum, M., Bergeron, ME., Ross, C., et al.[2022]

In vitro maturation (IVM) is a technique that allows immature oocytes to mature without the need for hormonal stimulation, making it a safer option for patients at high risk of ovarian hyperstimulation.

The results from IVM are comparable to standard IVF techniques, and there is currently no evidence of increased risk for fetal malformations, making it a suitable alternative for specific patients, particularly those with PCOS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro maturation (IVM) of human oocytes. Strowitzki, T.[2013]

In vitro maturation (IVM) is an effective technique for maturing immature oocytes, particularly beneficial for patients with polycystic ovary syndrome (PCOS) and those who do not respond well to traditional IVF treatments.

A case study demonstrated that IVM successfully salvaged an IVF cycle for a patient with poor response to gonadotrophin stimulation, suggesting its potential as a viable alternative for various patient profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro maturation may prevent the cancellation of in vitro fertilization cycles in poor responder patients: A case report. Yalçınkaya, E., Calışkan, E., Budak, O.[2021]

In vitro maturation (IVM) is a safer alternative to conventional IVF, particularly for patients at risk of ovarian hyperstimulation syndrome, with approximately 5000 live births reported since its inception.

While IVM shows lower live birth and implantation rates compared to conventional IVF, it significantly reduces the risk of ovarian hyperstimulation syndrome, making it a valuable option for carefully selected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro maturation and its role in clinical assisted reproductive technology. Sauerbrun-Cutler, MT., Vega, M., Keltz, M., et al.[2022]

The study found that a specific combination of 15 μg/ml selenium, 10 μg/ml calcium, and 5 μg/ml calcium ionophore resulted in the highest rates of human oocyte maturation (68% MII), development beyond the morula stage (20.1%), and blastocyst formation (11.1%).

The research suggests that adjusting intracellular ion concentrations can effectively trigger oocyte maturation and activation, indicating that these combinations could enhance in vitro maturation (IVM) protocols in assisted reproductive technologies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of selenium, calcium and calcium ionophore on human oocytes in vitro maturation in a chemically defined medium. Makki, M., Saboori, E., Sabbaghi, MA., et al.[2021]

In vitro maturation (IVM) is gaining recognition as a viable alternative to conventional in vitro fertilization (IVF), particularly in areas like fertility preservation and managing Ovarian Hyperstimulation Syndrome.

This systematic review highlights the extensive research supporting IVM's application across various fertility treatments, indicating its potential to be integrated more widely into assisted reproductive technology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oocyte in vitro maturation: A sytematic review. Hatırnaz, Ş., Ata, B., Hatırnaz, ES., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6823411/

Biphasic in vitro maturation (CAPA-IVM) specifically ... The primary outcomes were oocyte maturation, embryo quality, and the number of vitrified Day 3 embryos of good morphology, per patient.

2. academic.oup.com academic.oup.com/humrep/article-abstract/doi/10.1093/humrep/deaf097.1004/8170430

P-698 Comparison of Clinical Outcomes Between Biphasic ... The CAPA-IVM demonstrated significantly higher maturation rates (58.4% vs. 48.2%, p < 0.05) and normal fertilization rates (73.8% vs. 65.6%, p = ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0015028223001279

Outcomes of clinical in vitro maturation programs for ... This resulted in 4 ongoing pregnancies leading to the birth of a healthy child at term (overall rate of 5.3% per initiated cycle) (31). The other recently ...

4. medpharmres.com medpharmres.com/archive/view_article?pid=mpr-9-2-151

Biphasic in-vitro maturation: an advancement over ... Preliminary data also support normal developmental outcomes up to 24 months for children born after biphasic IVM. Biphasic IVM represents a promising ...

5. cureus.com cureus.com/articles/358217-successful-clinical-outcome-after-a-modified-protocol-of-rescue-in-vitro-maturation-of-oocytes-a-case-series-study

Successful Clinical Outcome After a Modified Protocol ... Overall, our work emphasizes the positive outcome of the use of Rescue-IVM technology, especially in patients with a low number of mature ...

6. asrm.org asrm.org/practice-guidance/practice-committee-documents/in-vitro-maturation-a-committee-opinion-2021/

In vitro maturation: a committee opinion (2021) Clinical pregnancy rates after fresh embryo transfer were highest when both FSH and hCG were used, 26.5%, compared with 11.8%, 5.4%, and 13.7% in the nonprimed, ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36754159/

Outcomes of clinical in vitro maturation programs for ... Data from nonrandomized studies generally showed either significantly low or statistically comparable rates of live birth with IVM vs. COS. Most studies have ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10664544/

In vitro maturation (IVM) of human immature oocytes In vitro maturation (IVM) of human immature oocytes has been shown to be a viable option for patients at risk of ovarian hyperstimulation syndrome (OHSS).

9. ajmb.org ajmb.org/Article?id=60581

Exploring the Potential of In vitro Maturation (IVM) of Oocytes The results of the meta-analysis indicated that IVM is an effective treatment option for women with PCOS who are trying to conceive 30. Yoon et al used IVM- ...