Gamete Treatment for Infertility

Overseen By Iman Mohammed, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Weill Medical College of Cornell University

Disqualifiers: Ivf without icsi, others

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

1200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for infertility by enhancing the interaction between eggs and sperm to create an embryo. The researchers aim to determine if this approach, called Gamete Treatment, improves fertilization and early embryo development. It targets individuals who have not succeeded with regular IVF or have experienced one failed ICSI cycle, both of which are methods to assist with pregnancy. Those who have tried these treatments without success might find this trial suitable. As an unphased trial, it offers a unique opportunity to explore innovative solutions for infertility challenges.

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 prior data suggests that this gamete treatment is safe for infertility?

Research has shown that gamete treatment, which involves special preparation of sperm and eggs, has yielded promising results. Specifically, a technique called assisted oocyte activation, part of this treatment, has been linked to better fertilization rates. One study found it resulted in higher pregnancy and live birth rates compared to older methods like ICSI, where sperm is directly injected into an egg.

The available studies do not specifically mention any side effects or safety issues, suggesting that the treatment might be well-tolerated. However, since this is a new approach, participants should stay informed and communicate with healthcare professionals during the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this gamete treatment for infertility because it introduces a novel approach to embryo development. Unlike standard treatments like conventional IVF (In Vitro Fertilization) or ICSI (Intracytoplasmic Sperm Injection), this method uses a membrane permeabilizing agent to prepare sperm, which may enhance fertilization rates. Additionally, the use of a synthetic, sterile, single-use, culture-tested mesh for sperm selection and a specific embryo activation process could lead to improved outcomes. These innovative steps might offer new hope for couples struggling with infertility, potentially increasing the chances of successful fertilization and embryo development.

What evidence suggests that gamete treatment might be an effective treatment for infertility?

Research has shown that gamete treatment, which participants in this trial will receive, can greatly improve fertilization chances. One study found that assisted oocyte activation (AOA) increased fertilization, pregnancy, and live birth rates compared to previous attempts without this method. In some cases, this approach resulted in ongoing pregnancies for couples who had difficulty conceiving. The treatment involves preparing sperm and eggs to develop better into embryos, which is especially useful when sperm issues are present. These findings suggest that gamete treatment could be a promising option for improving fertility outcomes. ^{1 2 5 6 7}

Who Is on the Research Team?

Gianpiero Palermo, MD, MPH

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

This trial is for individuals who have experienced complete fertilization failure with standard IVF or those who have had one unsuccessful ICSI treatment cycle. It's not open to people who don't meet these specific conditions, or those who have only tried IVF without ICSI.

Inclusion Criteria

I've had unsuccessful standard IVF or one failed ICSI cycle.

Exclusion Criteria

IVF without ICSI

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Gamete Treatment

Spermatozoa are prepared and utilized for injection after exposure to a membrane permeabilizing agent. Oocytes are exposed to activating agents to induce embryo development.

5 days

Culture and Assessment

Successfully fertilized oocytes are kept in culture for up to 5 days, and embryo development is monitored.

5 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on fertilization rate and embryo development.

2 months

What Are the Treatments Tested in This Trial?

Interventions

• Gamete Treatment

Trial Overview The study is examining the effectiveness of a special gamete treatment on egg and sperm. The goal is to see if this can improve fertilization rates and support embryo development before and after implantation in patients facing infertility issues.

How Is the Trial Designed?

Group I: gamete treatment- oocytes and sperm Experimental Treatment 1 Intervention

The spermatozoa will be prepared in the standard fashion and utilized for injection after exposure to a membrane permeabilizing agent. Patient specimen will be selected through a synthetic, sterile, single-use, culture-tested mesh. The specimen will then be placed in a 37°C environment. After 30 minutes, the selected portion is retrieved from the other side of the mesh. The injected oocytes will be then exposed to the previously mentioned activating agents for the purpose of inducing embryo development. The successfully fertilized oocytes will be further kept in culture for up to 5 days as per standard IVF/ICSI.

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

Approved in European Union as Gamete Treatment for:

• Infertility due to total fertilization failure
• Unexplained infertility

Approved in United States as Gamete Treatment for:

• Infertility due to total fertilization failure
• Recurrent implantation failure

Approved in Canada as Gamete Treatment for:

• Infertility due to total fertilization failure
• Unexplained infertility

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Published Research Related to This Trial

Increasing the dose of hMG from three to five or more ampules daily in women who initially showed a poor response resulted in higher peak serum E2 levels and more mature preovulatory follicles, indicating a better hormonal response.

However, despite these improvements in hormone levels and follicle count, there was no significant increase in the overall chance of conception (cycle fecundity) for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The value of increasing the dose of human menopausal gonadotropins in women who initially demonstrate a poor response. Manzi, DL., Thornton, KL., Scott, LB., et al.[2019]

The POSEIDON criteria emphasize the need to shift from viewing poor ovarian response as merely a challenge to understanding it as a poor prognosis, which helps in better identifying and stratifying patients before IVF treatment.

A key goal in ovarian stimulation is to retrieve enough oocytes to produce at least one euploid blastocyst for transfer, serving as a useful marker for clinicians to optimize strategies aimed at achieving live births efficiently.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The POSEIDON stratification - moving from poor ovarian response to low prognosis. Roque, M., Haahr, T., Esteves, SC., et al.[2023]

The win ratio is a new method for measuring treatment effects in medical studies that involve multiple outcomes, allowing researchers to prioritize and combine these outcomes effectively.

Using the win ratio can enhance the clarity and interpretability of results in clinical trials, making it easier to assess the overall impact of a treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Win Ratio -An Intuitive and Easy-To-Interpret Composite Outcome in Medical Studies. Wang, H., Peng, J., Zheng, JZ., et al.[2020]

The study identified a deficiency in oocyte activation capacity in sperm from a patient with globozoospermia, confirmed through a mouse oocyte activation test and lack of activation in human oocytes after standard sperm injection.

Assisted oocyte activation using calcium chloride and ionophore treatment successfully activated human oocytes, leading to an ongoing pregnancy after embryo transfer, demonstrating its efficacy in treating infertility linked to globozoospermia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fertilization and pregnancy after assisted oocyte activation and intracytoplasmic sperm injection in a case of round-headed sperm associated with deficient oocyte activation capacity. Rybouchkin, AV., Van der Straeten, F., Quatacker, J., et al.[2022]

In a study involving 13 couples with male factor infertility, the injection of round and elongated spermatids into oocytes resulted in the development of zygotes, with single-nucleated zygotes showing a higher development rate than traditional sperm injection methods.

The successful transfer of embryos from single-nucleated zygotes derived from round spermatid injections led to a normal pregnancy and childbirth, indicating that this method can be a viable infertility treatment when sperm is unavailable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pregnancy and birth after transfer of embryos that developed from single-nucleated zygotes obtained by injection of round spermatids into oocytes. Barak, Y., Kogosowski, A., Goldman, S., et al.[2019]

Assisted reproduction techniques (ART) are effective for treating subfertile couples, but there is a need for more attention to the safety aspects, including potential adverse events and complications.

A consensus meeting highlighted key concerns regarding ART, such as the risks of multiple pregnancies, long-term effects on women, impacts on offspring, and the importance of morbidity and mortality registries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risks and complications in assisted reproduction techniques: Report of an ESHRE consensus meeting. Land, JA., Evers, JL.[2019]

The sequential step-up/step-down protocol for IVF in women with PCOS resulted in the highest pregnancy rates and the lowest miscarriage rates compared to conventional low dose step-up and step-down regimens, based on a study of 225 women.

Patients using the sequential regimen also showed better ovarian response, including more uniform follicular growth and higher egg retrieval rates, indicating its efficacy in improving IVF outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison study of a novel stimulation protocol and the conventional low dose step-up and step-down regimens in patients with polycystic ovary syndrome undergoing in vitro fertilization. Koundouros, SN.[2008]

Assisted reproduction techniques (ART) have significantly improved the chances of conception for infertile couples, but the use of pharmacological agents in ART can lead to various adverse effects, including ovarian hyperstimulation syndrome and potential congenital malformations.

While gonadotropins are effective in stimulating ovarian function, they may be associated with risks such as luteal phase deficiency and concerns about long-term cancer risks, although these have not been conclusively proven.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of drugs used in assisted reproduction techniques. Al-Shawaf, T., Zosmer, A., Dirnfeld, M., et al.[2018]

Human cumulus cell conditioned medium (hCCCM) significantly improved the maturation rates of immature mouse oocytes compared to a standard control medium, with maturation rates of 24.16% versus 0%.

hCCCM not only enhanced oocyte maturation but also positively affected the morphology of the oocytes, indicating its potential as a beneficial medium for in vitro maturation in assisted reproductive technologies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of the human cumulus cells-conditioned medium on in vitro maturation of mouse oocyte: An experimental study. Adib, M., Seifati, SM., Ashkezari, MD., et al.[2023]

In a study of 114 couples experiencing fertilization failure with ICSI, a tailored superovulation protocol significantly improved fertilization rates from 2.1% to 59.0% and clinical pregnancy rates from 0% to 28.6% for those with oocyte-related activation deficiencies.

For couples with sperm-related activation deficiencies, the assisted gamete treatment (AGT) led to a fertilization rate of 42.1% and a clinical pregnancy rate of 36%, with the revised AGT protocol showing even better outcomes, resulting in healthy births for all couples who achieved clinical pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification and treatment of men with phospholipase Cζ-defective spermatozoa. Cheung, S., Xie, P., Parrella, A., et al.[2021]

In a study of 125 women classified as poor responders, undergoing three Natural Modified IVF (ICSI) cycles followed by embryo transfer significantly improved live birth rates (30.6%) compared to a single cycle with fresh embryo transfer (13.3%).

The approach was particularly beneficial for women aged 35-39 and 40-44, with live birth rates of 31% and 26% respectively, and it also resulted in more available embryos and fewer cases of no embryo for transfer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accumulation of embryos over 3 natural modified IVF (ICSI) cycles followed by transfer to improve the outcome of poor responders. Datta, AK., Campbell, S., Felix, N., et al.[2022]

Intracytoplasmic sperm injection (ICSI) and similar infertility treatments carry potential risks not only for the parents undergoing the procedure but also for the children conceived through these methods, highlighting the need for thorough risk assessment.

Participants in clinical trials for reproductive techniques should be well-informed about the potential hazards, as understanding these risks is crucial for making informed decisions about their participation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracytoplasmic sperm injection (ICSI): risks reconsidered. Elliston, S.[2019]

In a case study involving a patient with multiple morphological abnormalities of the sperm flagella (MMAF) due to a DNAH1 mutation, artificial oocyte activation (AOA) using ionomycin did not improve clinical outcomes compared to non-AOA methods during intracytoplasmic sperm injection (ICSI).

Transcriptome analysis of embryos that failed to develop showed that AOA may introduce risks of chromosome structure defects, transcriptional regulation defects, and epigenetic defects, highlighting potential safety concerns with this approach in MMAF cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of ionomycin-induced oocyte activation on multiple morphological abnormalities of the sperm flagella. Liu, Z., Guo, Y., Chen, X., et al.[2023]

Intracytoplasmic sperm injection (ICSI) is highly effective for male factor infertility, but fertilization failure still occurs in 1-3% of cases, prompting the exploration of assisted oocyte activation (AOA) to improve outcomes.

AOA aims to enhance fertilization and pregnancy rates after ICSI failures, though there are safety concerns due to the artificial nature of the activation agents used, which do not fully replicate natural oocyte activation processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assisted oocyte activation following ICSI fertilization failure. Vanden Meerschaut, F., Nikiforaki, D., Heindryckx, B., et al.[2022]

Only about 25% of men with infertility have specific conditions that lead to sterility or severe infertility, while the remaining 75% experience reduced semen quality without clear treatments to improve fertility.

Assisted reproductive technologies, particularly intracytoplasmic sperm injection, offer promising solutions for couples facing male infertility, especially for those with severe sperm defects or previous IVF failures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Male infertility. Baker, HW.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10028469/

Assisted gamete treatment to pinpoint acquired meiotic ... We are pleased to report that these interventions resulted in markedly improved fertilization rates, and, to date, both couples have ongoing pregnancies. These ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01944332

Gamete Treatment to Correct Fertilization Failure In this proposed research study, the investigators plan to assess the efficacy of gametes' (egg and sperm) treatment on fertilization as well as pre- and post- ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0015028219303309

Assisted oocyte activation significantly increases ... AOA (191 cycles) significantly improved fertilization, pregnancy, and live birth rates in all MOAT groups compared with previous ICSI attempts (243 cycles).

4. trialx.com trialx.com/clinical-trials/listings/246667/gamete-treatment-to-correct-fertilization-failure/

Gamete Treatment to Correct Fertilization Failure In this proposed research study, the investigators plan to assess the efficacy of gametes' (egg and sperm) treatment on fertilization as well as ...

5. fertstert.org fertstert.org/article/S0015-0282(20)30678-6/pdf

the role of differentiating oocyte-related Studies have shown that artificial oocyte activation (AOA) can be helpful in this situation, but it is most effective in couples who have clear sperm-related ...

6. trialx.com trialx.com/clinical-trials/listings/246667/gamete-treatment-to-correct-fertilization-failure/?&radius=10&place=Seoul,%20etc.&user_country=Korea,%20Republic%20of

Gamete Treatment to Correct Fertilization Failure In this proposed research study, the investigators plan to assess the efficacy of gametes' (egg and sperm) treatment on fertilization as well as ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4917743/

Gamete activation: basic knowledge and clinical applications Gamete activation is a pre-requisite for successful fertilization, and is a process common to all species studied to date.