PIMS vs PGT-A in Infertile PCOS Patients

Sun Yat-sen University

Status: Not yet enrolling

Conditions: PCOS; PIMS; PGT-A

Treatments: Genetic: PIMS screening; Genetic: PGT-A screening

Study type: Interventional

Funder types: Other

Identifiers

NCT06887881

[2024]345-2

Details and patient eligibility

About

This experiment has become a serious issue for two reasons: DNA methylation plays an important role during embryogenesis, global abnormal methylome reprogramming often occurs in human embryos, and DNA methylome pattern is associated with live birth rate. The endocrine metabolic disorders of polycystic ovarian syndrome (PCOS) patients may affect the epigenetic status of embryos and lead to the increase of early pregnancy loss rate in PCOS patients. However, there is still no technology using DNA methylome as an indicator in preimplantation embryo screening in PCOS patients. Our recent study showed that using Pre-implantation Methylation Screening (PIMS) can select embryos with better methylation state and euploid chromosomes. The efficiency of PIMS in PCOS patients needs further validation through randomized controlled clinical trial.

The purpose of the study is to compare whether the two groups of PCOS patients who selected embryos using PIMS and selected embryos using "PGT-A + morphology"had any difference in early pregnancy loss rate. This study aims to explore whether PIMS can be used as another embryo evaluation method besides "PGT-A+morphology" to screen good developmental potential embryos in patients with PCOS. Investigators need to clarify whether a better embryo evaluation system can be established through PIMS technology during assisted reproductive treatment for infertile PCOS couples and provide credible and effective evidence-based medical evidence for the application of PMIS technology in the field of reproductive medicine.

Enrollment: 766 estimated patients

Sex: Female

Ages: 20 to 40 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Women aged between 20 and 40 years diagnosed with PCOS according to international evidence-based guidline for assessment and management of policystic ovarian syndrome 2018.
2. Women who plan to undergo the 1st/2nd IVF/ICSI/PGT-A treatment cycle.
3. Women who obtain 2 or more blastocysts that have morphological score of 4BC/4CB or better on Day 5of embryo culture.
4. Culture all the cleavage stage embryos into blastocysts, conduct biopsy on all the blastocysts, and cryopreserve each blastocyst as a single embryo
5. Agree to the thawing and transfer of a single blastocyst.
6. Sign the informed consent form.

Exclusion criteria

1. Women with a uterine cavity abnormality, such as a uterine congenital malformation (uterus unicornate, bicornate, or duplex); untreated uterine septum, submucous myoma, or endometrial polyp(s); or with history of intrauterine adhesions.
2. Women who are indicated and planned to undergo preimplantation genetic testing for structural rearrangements (PGT-SR) or preimplantation genetic testing for monogenic (PGT-M).
3. Women who use donated oocytes or sperm to achieve pregnancy.
4. Women with contraindication for assisted reproductive technology or for pregnancy, such as undiagnosed liver disease or dysfunction (based on serum liver enzyme testing); renal disease or abnormal serum renal function; significant anemia; history of deep venous thrombosis, pulmonary embolus, or cerebrovascular accident; uncontrolled hypertension, known symptomatic heart disease; history of or suspected carcinoma including including cervical carcinoma, endometrial carcinoma, or breast carcinoma; undiagnosed vaginal bleeding and so on.
5. Untreated hydrosalpinx according to ultrasonography test.

Trial design

Primary purpose: Screening

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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766 participants in 2 patient groups

PIMS Group

Experimental group

Description:

Couples in the PIMS group will have up to 6 blastocysts screened with PIMS and a single euploid embryo with the optimal state of whole-genome DNA methylation and the highest morphologic score will be selected for the initial transfer. The optimal state of whole-genome DNA methylation includes methylation level closest to the optimal level (0.26 according to our preliminary results) and proper methylation state for some specific regions.Blastocysts that have undergone a second biopsy will not be preferred.

Treatment:

Genetic: PIMS screening

PGT-A Group

Active Comparator group

Description:

Couples in the PGT-A group will have up to 6 blastocysts screened with PGT-A and a single euploid blastocyst with the highest morphologic score selected for the initial transfer.Blastocysts that have undergone a second biopsy will not be preferred.

Treatment:

Genetic: PGT-A screening