Genetic Testing for Infertility

(GETSET Trial)

Overseen By Kristin Rooney

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: Genomic Prediction Inc.

Disqualifiers: Donor oocytes, Gestational carrier, RPL, others

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

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

Compensation: Varies

Number of Visits: Unknown

240 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether genetic testing of embryos before implantation can improve pregnancy outcomes for women undergoing IVF. It compares two approaches: transferring embryos with tested normal chromosomes (Preimplantation Genetic Testing for Aneuploidy, or PGT-A) versus untested embryos. The researchers aim to determine if genetic testing aids in selecting the healthiest embryos for implantation in women ages 35 to 40 undergoing IVF. Women who have been trying IVF with their own or donor sperm, but not donor eggs, might find this trial relevant. As an unphased trial, this study offers a unique opportunity to contribute to understanding the potential benefits of genetic testing in IVF.

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 preimplantation genetic testing for aneuploidy (PGT-A) is safe?

Research has shown that preimplantation genetic testing for aneuploidy (PGT-A) is generally safe and well-tolerated. This test checks embryos for genetic issues before placement in the uterus. Past studies have found no major safety problems for women undergoing this procedure. The test focuses on the embryos, and participants usually do not report significant side effects from the testing itself.

While PGT-A is used to select embryos that might lead to a successful pregnancy, studies have not consistently demonstrated a clear improvement in overall pregnancy outcomes. However, the procedure itself is considered safe. Thus, the main question about PGT-A concerns its effectiveness, rather than its safety. Participants considering joining a trial involving PGT-A can feel reassured by the existing safety information. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about preimplantation genetic testing for aneuploidy (PGT-A) because it offers a more precise way to select embryos for IVF. Unlike traditional methods which rely on visual assessment of embryos, PGT-A uses advanced genetic testing to identify embryos with the correct number of chromosomes, known as euploid embryos. This approach could potentially increase the chances of a successful pregnancy by transferring the best quality, genetically normal embryos. This method could also reduce the likelihood of miscarriage and improve overall IVF success rates, making it a promising advancement for couples facing infertility challenges.

What evidence suggests that preimplantation genetic testing for aneuploidy (PGT-A) might be an effective treatment for infertility?

Research has shown that preimplantation genetic testing for aneuploidy (PGT-A), which participants in this trial may receive, can improve pregnancy outcomes for women undergoing IVF. This testing identifies embryos with the correct number of chromosomes, reducing the risk of miscarriage. One study found that using PGT-A significantly reduced pregnancy loss, with an odds ratio of 0.42, indicating its effectiveness compared to not using the test. Another study indicated that PGT-A can lead to higher live birth rates by selecting embryos more likely to result in successful pregnancies. Overall, PGT-A helps in choosing embryos with a better chance of leading to a healthy pregnancy. ^{1 4 6 7 8}

Who Is on the Research Team?

Nathan Treff, PhD

Principal Investigator

Genomic Prediction Clinical Labortory

Are You a Good Fit for This Trial?

The GETSET trial is for women aged 35-40 undergoing IVF with their own or donor sperm, and any COH protocol. It's not for those using donor eggs, gestational carriers, have had ≥3 miscarriages in a row, ≥3 failed embryo transfers, need genetic testing for single gene disorders or are translocation carriers.

Inclusion Criteria

I am using my own or donor sperm for treatment.

I am undergoing or have undergone ovarian stimulation treatment.

I am using or plan to use ICSI or traditional IVF for conception.

Exclusion Criteria

I have undergone genetic testing for specific inherited disorders.

I have had 3 or more unsuccessful embryo transfers.

I have a genetic change known as a translocation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Ovarian Hyper-stimulation and Embryo Culture

Participants undergo ovarian hyper-stimulation, oocyte retrieval, fertilization, and embryo culture per standard clinical protocol

4-6 weeks

Embryo Transfer

Participants undergo a single frozen embryo transfer of the best quality blastocyst

1 week

Follow-up

Participants are monitored for pregnancy outcomes, including miscarriage and ongoing pregnancy rates

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Preimplantation genetic testing for aneuploidy (PGT-A)

Trial Overview This study tests if preimplantation genetic testing for aneuploidies (PGT-A) improves pregnancy outcomes when used during elective single embryo transfer in IVF treatments for women between the ages of 35 and 40.

How Is the Trial Designed?

Group I: Experimental Arm - Transfer of Best Quality, Euploid Blastocyst Experimental Treatment 1 Intervention

Transfer of best quality, PGTA normal (euploid) blastocyst.

Group II: Control Arm - Transfer of Untested, Best Quality Blastocyst Active Control 1 Intervention

Transfer of Untested, Best Quality Blastocyst

Preimplantation genetic testing for aneuploidy (PGT-A) is already approved in United States, European Union for the following indications:

Approved in United States as PGT-A for:

• Screening for aneuploidy in embryos generated through IVF

Approved in European Union as PGT-A for:

• Screening for aneuploidy in embryos generated through IVF

Who Is Running the Clinical Trial?

Genomic Prediction Inc.

Lead Sponsor

Trials

6

Recruited

11,700+

Boston IVF

Collaborator

Trials

21

Recruited

21,400+

Published Research Related to This Trial

Preimplantation genetic testing for aneuploidy (PGT-A) in older women (aged ≥37 years) undergoing assisted reproductive technology resulted in a cumulative live-birth rate of 30.90%, compared to 26.77% for morphological assessment (MA) of embryos, indicating that PGT-A may improve live-birth outcomes.

The study found that PGT-A had an incremental cost-effectiveness ratio of $28,103 per additional live birth, suggesting that it is cost-effective at a willingness-to-pay threshold of $50,000, with over 80% probability of being cost-effective from a healthcare perspective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A cost-effectiveness analysis of preimplantation genetic testing for aneuploidy (PGT-A) for up to three complete assisted reproductive technology cycles in women of advanced maternal age. Lee, E., Costello, MF., Botha, WC., et al.[2020]

Preimplantation genetic testing for aneuploidy screening (PGT-A) is designed to improve the chances of a live birth per embryo transfer while reducing risks like miscarriage and aneuploid pregnancies, but it may not necessarily increase the cumulative live birth rate (CLBR) for all patients, particularly younger ones.

Recent studies suggest that while PGT-A can help select healthier embryos, it may inadvertently lower the overall CLBR, highlighting the need to carefully consider its benefits and risks in the context of in-vitro fertilization cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does PGT-A affect cumulative live birth rate? Seckin, S., Forman, EJ.[2023]

In a study of 60,580 patients undergoing IVF, preimplantation genetic testing for aneuploidy (PGT-A) did not improve the cumulative live birth rate (CLBR) compared to standard IVF, showing a CLBR of 27.5% for PGT-A users versus 31.1% for non-PGT-A users.

However, PGT-A users experienced significantly higher rates of successful first embryo transfers (63.9% vs. 46.9%) and live births (52.6% vs. 34.2%), along with lower rates of early miscarriage, preterm birth, and low birth weight, indicating its effectiveness for certain populations, particularly women over 38 or those with recurrent pregnancy loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring the efficacy and beneficial population of preimplantation genetic testing for aneuploidy start from the oocyte retrieval cycle: a real-world study. Ma, S., Liao, J., Zhang, S., et al.[2023]

Chromosomal aneuploidy is a major cause of implantation failure and miscarriage, significantly impacting the success rates of in vitro fertilization (IVF).

Preimplantation genetic testing for aneuploidy (PGT-A) using next generation sequencing (NGS) improves embryo selection for transfer, enhancing the success of assisted reproductive technology (ART) cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aneuploidy Screening using Next Generation Sequencing. Cinnioglu, C., Kayali, R., Darvin, T., et al.[2019]

Preimplantation genetic testing for aneuploidy (PGT-A) helps improve IVF outcomes by screening embryos for chromosomal abnormalities, particularly benefiting older mothers by reducing the negative effects of age on fertility.

The emergence of mosaic aneuploid embryos after PGT-A raises concerns, as these embryos carry risks such as miscarriage and fetal complications; a risk score system has been developed to guide decisions on which mosaic embryos to transfer, but long-term outcomes remain unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of preimplantation genetic testing for aneuploidy on obstetrical practice. Chan, YM., Li, TC., Poon, LCY.[2020]

Preimplantation genetic testing for aneuploidy (PGT-A) significantly improves clinical outcomes in recurrent pregnancy failure (RPF) patients, with higher implantation rates, clinical pregnancy rates, ongoing pregnancy rates, and live birth rates compared to those not undergoing PGT-A.

The analysis of 13 studies involving 930 RPF patients undergoing PGT-A and over 1,434 without it showed that PGT-A also resulted in a lower clinical miscarriage rate, indicating its potential benefits in enhancing successful pregnancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis: clinical outcomes of recurrent pregnancy failure resulting from preimplantation genetic testing for aneuploidy. Liang, Z., Wen, Q., Li, J., et al.[2023]

Preimplantation genetic testing for aneuploidy (PGT-A) has become increasingly important in improving live birth rates during IVF by screening embryos for chromosomal abnormalities.

While PGT-A can help identify embryos with potential aneuploidy, it is important to note that it cannot definitively predict the chromosomal status of the embryo or fetus, highlighting the limitations of this screening method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive prenatal testing in the context of IVF and PGT-A. Kimelman, D., Pavone, ME.[2021]

A study involving 7146 live births from IVF/ICSI cycles found that preimplantation genetic testing for aneuploidy (PGT-A) does not lead to increased rates of adverse maternal and neonatal outcomes in singleton pregnancies, suggesting its safety in this context.

While initial analyses indicated higher risks of pre-eclampsia and cesarean sections in PGT-A pregnancies, further statistical adjustments showed no significant differences in adverse outcomes, and a subgroup analysis revealed a decreased risk of preterm birth for pregnancies involving blastocysts screened with next-generation sequencing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preimplantation genetic testing for aneuploidy is not related to adverse obstetric and neonatal outcomes in singleton pregnancies. Cozzolino, M., Cecchino, GN., Garcia Velasco, JA., et al.[2023]

Preimplantation genetic testing for aneuploidy (PGT-A) has shown promise in improving pregnancy outcomes, particularly by reducing miscarriage rates and decreasing time to delivery in patients with diminished ovarian reserve or poor response to stimulation.

Initial studies suggest that PGT-A can be beneficial for 'poor responders' in IVF, but more research is needed to understand the different subpopulations within this group and to optimize the use of PGT-A across various clinical scenarios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The dilemma of aneuploidy screening on low responders. Morin, SJ., Kaser, DJ., Franasiak, JM.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10914495/

Clinical outcomes of preimplantation genetic testing for ... The purpose of this study was to evaluate the impact of preimplantation genetic testing for aneuploidy (PGT-A) on clinical outcomes among high-risk patients.

2. mdpi.com mdpi.com/2077-0383/13/20/6192?

Preimplantation Genetic Testing for Aneuploidy (PGT-A) in ... Introduction: Poor outcomes following IVF treatments are speculated to be due to the transfer of aneuploid embryos that cannot be identified based on ...

3. asrm.org asrm.org/practice-guidance/practice-committee-documents/the-use-of-preimplantation-genetic-testing-for-aneuploidy-a-committee-opinion-2024/

The use of preimplantation genetic testing for aneuploidy The primary outcome of ongoing pregnancy beyond 20 weeks per transfer was similar between the study and control groups (60.7% [54/89] vs. 65.1% [56/86]). The ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2103613

Live Birth with or without Preimplantation Genetic Testing ... Embryo selection with preimplantation genetic testing for aneuploidy (PGT-A) may improve pregnancy outcomes after initial embryo transfer.

5. fertstert.org fertstert.org/article/S0015-0282(24)01957-5/fulltext

Preimplantation genetic testing for aneuploidy in ... Preimplantation genetic testing for aneuploidy decreased clinical pregnancy loss rate (OR, 0.42; 95% CI, 0.27–0.67) and enhanced LBR per ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7125263/

Preimplantation genetic testing for aneuploidy (PGT-A) The STAR study thus reveals that PGT-A does not beneficially affect IVF outcomes in confirmation of another relatively recent study in women 37 years and older.

7. hfea.gov.uk hfea.gov.uk/treatments/treatment-add-ons/pre-implantation-genetic-testing-for-aneuploidy-pgt-a/

Pre-implantation genetic testing for aneuploidy (PGT-A) The use of PGT-A is rated grey for improving the chances of having a baby in older women. This is because there is insufficient moderate/high quality evidence ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S001502822500216X

The impact of preimplantation genetic testing for ... Preimplantation genetic testing for aneuploidy is associated with a shorter time to pregnancy resulting in a live birth for patients who are at least 38 years ...