P-579 Factors that influence the outcome of Pre-Implantation Genetic Testing for Monogenic Disease (PGT-M) and Pre-Implantation Genetic Testing for Aneuploidy (PGT-A). A five year analysis

Study question

What factors influence the treatment outcomes of PGT-M with concurrent PGT-A?

Summary answer

Advancing female age, history of subfertility reduce the chance of live birth (LB). Anti-Mullerian Hormone (AMH) had a positive correlation with the chance of LB.

What is known already

Single gene disorders can affect approximately one in every 250 births. As most of these conditions have limited treatment and no cure, PGT-M testing is an important and widely used method to prevent patients having children with a single gene disorder. Currently, in the UK, there are over 1700 single gene disorders with HFEA regulatory license for use of PGT-M to aid embryo selection.

There remains limited evidence available on concurrent use of PGT-A during PGT-M and limited data on the factors affecting reproductive outcome. Data centred discussions are an essential step in pre-treatment counselling in order to manage patients’ expectations.

Study design, size, duration

We retrospectively studied 417 ovarian stimulation treatment cycles performed on 266 patients who underwent PGT-M between January 2019 and May 2024 in a single Fertility Centre in the UK. Controlled ovarian stimulation was undertaken with GnRH agonist or GnRH antagonist protocol. Intracytoplasmic injection was undertaken for insemination and trophectoderm biopsy was performed on day 5 or day 6 blastocysts. Following PGT M, those found to be unaffected by the single gene disorder underwent concurrent PGT-A.

Participants/materials, setting, methods

All PGT-M cycles during the study period were included except egg thaw cycles.

Clinical pregnancy was defined as ultrasound visualisation of a fetus with heart activity five weeks after frozen embryo replacement. Ongoing pregnancies were included in the live birth rate calculation. Multivariate regression analysis was performed to assess the effect of age, previous history of subfertility and AMH on clinical pregnancy rate (CPR) and live birth rate (LBR).

Main results and the role of chance

The female age ranged from 23-43 years with a median age of 32 (SD:3.7).

16.5%(44/266) of patients had a documented history of subfertility. 7.1% of females had an AMH value below 5 pmol/L.

417 ovarian stimulation treatment cycles resulted in 4987 collected mature oocytes. 1977 embryos were suitable for trophectoderm biopsy. 1070 biopsied embryos were found to be unaffected or carriers. 63% (676/1070) of the unaffected or carrier embryos were found to be euploid or low level mosaic. 311 frozen embryo replacements of unaffected, euploid embryos were completed using a natural or medicated approach.

Clinical pregnancy rate per embryo transfer was 64%, Live birth rate per transfer was 56.7%.

Couples with a previous history of subfertility had lower odds of a live birth (OR:0.37 95% CI:0.33-0.43), the odds of live birth was 1.73 times higher for females with AMH of greater than 5 pmol/L compared to AMH less than 5 pmol/L (OR 1.73 95% CI 1.21-2.51). Each year of advancing female age resulted in a reduction in odds of a livebirth (OR:0.92 95% CI 0.91-0.93) when adjusting for other variables.

Limitations, reasons for caution

This study was a retrospective study, though our laboratory and clinical practices has not changed to a great degree during the five year study period.

Wider implications of the findings

The above findings are important when considering pre-treatment counselling to help patients make informed decisions regarding their clinical care. This enables effective management of expectations. The impact of female age and AMH on treatment outcomes emphasise the importance of timely fertility treatment in those considering PGT-M with concurrent PGT-A. .

Trial registration number

No