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

Summary This study analyzed the effects of the day of trophectoderm (TE) biopsy and blastocyst grade on clinical and neonatal outcomes. The results showed that the implantation and live birth rates of day 5 (D5) TE biopsy were significantly higher compared with those of D6 TE biopsy. The miscarriage rate of the former was lower than that of the latter, but there was no statistically significant difference. Higher quality blastocysts can achieve better implantation and live birth rates. Among good quality blastocysts, the implantation and live birth rates of D5 and D6 TE biopsy were not significantly different. Among fair quality and poor quality blastocysts, the implantation and live birth rates of D5 TE biopsy were significantly higher compared with those of D6 TE biopsy. Neither blastocyst grade nor the day of TE biopsy significantly affected the miscarriage rate. Neonatal outcomes, including newborn sex, gestational age, preterm birth, birth weight and low birth weight in the D5 and D6 TE biopsies were not significantly different. Both blastocyst grade and the day of TE biopsy must be considered at the same time when performing preimplantation genetic testing–frozen embryo transfer.

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IVF COVERAGE IN MANDATED VS. NON-MANDATED STATES ALLOWS FOR HIGHER LIVE BIRTH RATES BUT NOT INCREASED USAGE OF PREIMPLANTATION GENETIC TESTING FOR ANEUPLOIDY (PGT-A)

Fertility and Sterility ◽

10.1016/j.fertnstert.2021.05.060 ◽

2021 ◽

Vol 116 (1) ◽

pp. e39

Author(s):

Michelle Kappy ◽

Tracy Ngo ◽

Julian Gingold ◽

Sangita Jindal ◽

Susan Klugman ◽

...

Keyword(s):

Genetic Testing ◽

Live Birth ◽

Birth Rates ◽

Preimplantation Genetic Testing ◽

Live Birth Rates

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In unexplained recurrent pregnancy loss, daily LMWH did not improve ongoing pregnancy or live birth rates

Annals of Internal Medicine ◽

10.7326/acpjc-2015-163-6-010 ◽

2015 ◽

Vol 163 (6) ◽

pp. JC10 ◽

Cited By ~ 1

Author(s):

Alexander Gallus

Keyword(s):

Live Birth ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Ongoing Pregnancy ◽

Birth Rates ◽

Live Birth Rates

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P-377 Association between antinuclear antibodies and pregnancy prognosis in recurrent pregnancy loss patients

Human Reproduction ◽

10.1093/humrep/deab127.069 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

H Yoshihara ◽

M Sugiura-Ogasawara ◽

T Kitaori ◽

S Goto

Keyword(s):

Live Birth ◽

Pregnancy Loss ◽

Birth Rate ◽

Recurrent Pregnancy Loss ◽

Live Birth Rate ◽

Negative Group ◽

Birth Rates ◽

Positive Group ◽

Live Birth Rates ◽

Uterine Anomaly

Abstract Study question Can antinuclear antibody (ANA) affect the subsequent live birth rate in patients with recurrent pregnancy loss (RPL) who have no antiphospholipid antibodies (aPLs)? Summary answer ANA did not affect the pregnancy prognosis of RPL women. What is known already The prevalence of ANA is well-known to be higher in RPL patients. Our previous study found no difference in the live birth rates of ANA-positive and -negative patients who had no aPLs. Higher miscarriage rates were also reported in ANA-positive patients compared to ANA-negative patients with RPL. The RPL guidelines of the ESHRE state that “ANA testing can be considered for explanatory purposes.” However, there have been a limited number of studies on this issue and sample sizes have been small, and the impact of ANA on the pregnancy prognosis is unclear. Study design, size, duration An observational cohort study was conducted at Nagoya City University Hospital between 2006 and 2019. The study included 1,108 patients with a history of 2 or more pregnancy losses. Participants/materials, setting, methods 4D-Ultrasound, hysterosalpingography, chromosome analysis for both partners, aPLs and blood tests for ANA and diabetes mellitus were performed before a subsequent pregnancy. ANAs were measured by indirect immunofluorescence. The cutoff dilution used was 1:40. In addition, patients were classified according to the ANA pattern on immunofluorescence staining. Live birth rates were compared between ANA-positive and ANA-negative patients after excluding patients with antiphospholipid syndrome, an abnormal chromosome in either partner and a uterine anomaly. Main results and the role of chance The 994 patients were analyzed after excluding 40 with a uterine anomaly, 43 with a chromosome abnormality in either partner and 32 with APS. The rate of ANA-positive patients was 39.2 % (390/994) when the 1: 40 dilution result was positive. With a 1:160 dilution, the rate of ANA-positive patients was 3.62 % (36/994). The live birth rate was calculated for 798 patients, excluding 196 patients with unexplained RPL who had been treated with any medication. With the use of the 1 40 dilution, the subsequent live birth rates were 71.34 % (219/307) for the ANA-positive group and 70.67 % (347/491) for the ANA-negative group (OR, 95%CI; 0.968, 0.707-1.326). After excluding miscarriages with embryonic aneuploidy, chemical pregnancies and ectopic pregnancies, live birth rates were 92.41 % (219/237) for the ANA-positive group and 92.04 % (347/377) for the ANA-negative group (0.951, 0.517-1.747). Using the 1:160 dilution, the subsequent live birth rates were 84.62 % (22/26) for the ANA-positive group, and 70.47 % (544/772) for the ANA-negative group (0.434, 0.148-1.273). Subgroup analyses were performed for each pattern on immunofluorescence staining, but there was no significant difference in the live birth rate between the two groups. Limitations, reasons for caution The effectiveness of immunotherapies could not be evaluated. However, the results of this study suggest that it is not necessary. Wider implications of the findings The measurement of ANA might not be necessary for the screening of patients with RPL who have no features of collagen disease. Trial registration number not applicable

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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

Human Reproduction ◽

10.1093/humrep/dez229 ◽

2019 ◽

Vol 34 (12) ◽

pp. 2340-2348 ◽

Cited By ~ 11

Author(s):

Takeshi Sato ◽

Mayumi Sugiura-Ogasawara ◽

Fumiko Ozawa ◽

Toshiyuki Yamamoto ◽

Takema Kato ◽

...

Keyword(s):

Live Birth ◽

Pregnancy Loss ◽

Birth Rate ◽

Recurrent Pregnancy Loss ◽

Live Birth Rate ◽

Not Given ◽

Recurrent Implantation Failure ◽

Miscarriage Rate ◽

Preimplantation Genetic Testing ◽

Biochemical Pregnancy

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 N/A

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Pregnancy outcomes among patients with recurrent pregnancy loss and chromosomal aberration (CA) without PGD

Journal of Perinatal Medicine ◽

10.1515/jpm-2016-0408 ◽

2018 ◽

Vol 46 (7) ◽

pp. 764-770 ◽

Cited By ~ 4

Author(s):

Maor Kabessa ◽

Avi Harlev ◽

Michael Friger ◽

Ruslan Sergienko ◽

Baila Litwak ◽

...

Keyword(s):

Live Birth ◽

Pregnancy Outcomes ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Control Group ◽

Study Group ◽

Birth Rates ◽

Live Birth Rates ◽

Index Pregnancy ◽

Significant Difference

Abstract Background: Recurrent pregnancy loss (RPL) is defined by two or more failed clinical pregnancies. Three to four percent of the couples with RPL have chromosomal aberrations (CA) in at least one partner. The parent’s structural chromosomal abnormalities may cause an unbalanced karyotype in the conceptus which could lead to implantation failure, early or late pregnancy loss, or delivery of a child with severe physical and/or mental disabilities. Objective: To compare live birth rates of couples with CA to couples with normal karyotypes and to investigate medical and obstetric characteristics and pregnancy outcomes of couples with CA and RPL who attend an RPL clinic at a tertiary hospital. Methods: A retrospective cohort study, including 349 patients with two or more consecutive pregnancy losses. The study group consisted of 52 patients with CA, and the control group consisted of 297 couples with normal karyotype. All patients were evaluated and treated in the RPL clinic at Soroka University Medical Center and had at least one subsequent spontaneous pregnancy. Results: The demographic and clinical characteristics were not found to be statistically different between the two groups. The group of carriers of CA had 28/52 (53.8%) live births in their index pregnancy vs. the normal 202/297 (68%) (P=0.067, CI 95%) in the control group. No statistically significant etiology was found between the study group and the control group. A statistically significant difference in live birth rates was found when comparing the total amount of pregnancies [index pregnancy (IP)+post index pregnancy (PIP)] between the study group and the control group (54.16% vs. 67.82%, respectively, P=0.0328). Conclusion: Patients with RPL and CA who have spontaneous pregnancies, have a good prognosis (63.4%) of a successful pregnancy with at least one of the pregnancies (index or post index) resulting in a live birth.

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Preimplantation Genetic Testing for Aneuploidy Improves Live Birth Rates with In Vitro Produced Bovine Embryos: A Blind Retrospective Study

Cells ◽

10.3390/cells10092284 ◽

2021 ◽

Vol 10 (9) ◽

pp. 2284

Author(s):

Giuseppe Silvestri ◽

Carla Canedo-Ribeiro ◽

María Serrano-Albal ◽

Remi Labrecque ◽

Patrick Blondin ◽

...

Keyword(s):

Genetic Testing ◽

Live Birth ◽

Bovine Embryos ◽

Birth Rates ◽

Preimplantation Genetic Testing ◽

Live Birth Rates ◽

Snp Data ◽

Donor Chromosome ◽

Estimated Breeding Values

Approximately one million in vitro produced (IVP) cattle embryos are transferred worldwide each year as a way to improve the rates of genetic gain. The most advanced programmes also apply genomic selection at the embryonic stage by SNP genotyping and the calculation of genomic estimated breeding values (GEBVs). However, a high proportion of cattle embryos fail to establish a pregnancy. Here, we demonstrate that further interrogation of the SNP data collected for GEBVs can effectively remove aneuploid embryos from the pool, improving live births per embryo transfer (ET). Using three preimplantation genetic testing for aneuploidy (PGT-A) approaches, we assessed 1713 cattle blastocysts in a blind, retrospective analysis. Our findings indicate aneuploid embryos have a 5.8% chance of establishing a pregnancy and a 5.0% chance of given rise to a live birth. This compares to 59.6% and 46.7% for euploid embryos (p < 0.0001). PGT-A improved overall pregnancy and live birth rates by 7.5% and 5.8%, respectively (p < 0.0001). More detailed analyses revealed donor, chromosome, stage, grade, and sex-specific rates of error. Notably, we discovered a significantly higher incidence of aneuploidy in XY embryos and, as in humans, detected a preponderance of maternal meiosis I errors. Our data strongly support the use of PGT-A in cattle IVP programmes.

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