Preimplantation genetic testing for aneuploidy: a comparison of live birth rates in patients with recurrent pregnancy loss due to embryonic aneuploidy or recurrent implantation failure
Authors: Sato Takeshi , Sugiura-Ogasawara Mayumi , Ozawa Fumiko , Yamamoto Toshiyuki , Kato Takema , Kurahashi Hiroki , Kuroda Tomoko , Aoyama Naoki , Kato Keiichi , Kobayashi Ryota , Fukuda Aisaku , Utsunomiya Takafumi , Kuwahara Akira , Saito Hidekazu , Takeshita Toshiyuki , Irahara Minoru 
Published: October 2019

Abstract

STUDY QUESTION
Can preimplantation genetic testing for aneuploidy (PGT-A) improve the live birth rate and reduce the miscarriage rate in patients with recurrent pregnancy loss (RPL) caused by an abnormal embryonic karyotype and recurrent implantation failure (RIF)?

SUMMARY ANSWER
PGT-A could not improve the live births per patient nor reduce the rate of miscarriage, in both groups.

WHAT IS KNOWN ALREADY
PGT-A use has steadily increased worldwide. However, only a few limited studies have shown that it improves the live birth rate in selected populations in that the prognosis has been good. Such studies have excluded patients with RPL and RIF. In addition, several studies have failed to demonstrate any benefit at all. PGT-A was reported to be without advantage in patients with unexplained RPL whose embryonic karyotype had not been analysed. The efficacy of PGT-A should be examined by focusing on patients whose previous products of conception (POC) have been aneuploid, because the frequencies of abnormal and normal embryonic karyotypes have been reported as 40–50% and 5–25% in patients with RPL, respectively.

STUDY DESIGN, SIZE, DURATION
A multi-centre, prospective pilot study was conducted from January 2017 to June 2018. A total of 171 patients were recruited for the study: an RPL group, including 41 and 38 patients treated respectively with and without PGT-A, and an RIF group, including 42 and 50 patients treated respectively with and without PGT-A. At least 10 women in each age group (35–36, 37–38, 39–40 or 41–42 years) were selected for PGT-A groups.

PARTICIPANTS/MATERIALS, SETTING, METHODS
All patients and controls had received IVF-ET for infertility. Patients in the RPL group had had two or more miscarriages, and at least one case of aneuploidy had been ascertained through prior POC testing. No pregnancies had occurred in the RIF group, even after at least three embryo transfers. Trophectoderm biopsy and array comparative genomic hybridisation (aCGH) were used for PGT-A. The live birth rate of PGT-A and non-PGT-A patients was compared after the development of blastocysts from up to two oocyte retrievals and a single blastocyst transfer. The miscarriage rate and the frequency of euploidy, trisomy and monosomy in the blastocysts were noted.

MAIN RESULT AND THE ROLE OF CHANCE
There were no significant differences in the live birth rates per patient given or not given PGT-A: 26.8 versus 21.1% in the RPL group and 35.7 versus 26.0% in the RIF group, respectively. There were also no differences in the miscarriage rates per clinical pregnancies given or not given PGT-A: 14.3 versus 20.0% in the RPL group and 11.8 versus 0% in the RIF group, respectively. However, PGT-A improved the live birth rate per embryo transfer procedure in both the RPL (52.4 vs 21.6%, adjusted OR 3.89; 95% CI 1.16–13.1) and RIF groups (62.5 vs 31.7%, adjusted OR 3.75; 95% CI 1.28–10.95). Additionally, PGT-A was shown to reduce biochemical pregnancy loss per biochemical pregnancy: 12.5 and 45.0%, adjusted OR 0.14; 95% CI 0.02–0.85 in the RPL group and 10.5 and 40.9%, adjusted OR 0.17; 95% CI 0.03–0.92 in the RIF group. There was no difference in the distribution of genetic abnormalities between RPL and RIF patients, although double trisomy tended to be more frequent in RPL patients.

LIMITATIONS, REASONS FOR CAUTION
The sample size was too small to find any significant advantage for improving the live birth rate and reducing the clinical miscarriage rate per patient. Further study is necessary.

WIDER IMPLICATION OF THE FINDINGS
A large portion of pregnancy losses in the RPL group might be due to aneuploidy, since PGT-A reduced the overall incidence of pregnancy loss in these patients. Although PGT-A did not improve the live birth rate per patient, it did have the advantage of reducing the number of embryo transfers required to achieve a similar number live births compared with those not undergoing PGT-A.

STUDY FUNDING/COMPETING INTEREST(S)
This study was supported by the Japan Society of Obstetrics and Gynecology and grants from the Japanese Ministry of Education, Science, and Technology. There are no conflicts of interest to declare.

TRIAL REGISTRATION NUMBER
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