Effects of PGS2.0 in Patients With Unexplained RPL

Infertility, Female Clinical Trial

Official title:

Effects of Preimplantation Genetic Screening 2.0 on the Clinical Outcomes of Assisted Reproductive Treatment in Patients With Recurrent Pregnancy Loss : A Multi-center-based Prospective Randomized Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03214185
• Other study ID #: JIAI E2017-15
• Status: Recruiting
• Phase: N/A
• First received: July 9, 2017
• Last updated: February 4, 2018
• Start date: February 6, 2018
• Est. completion date: September 30, 2021

Study information

• Verified date: July 2017
• Source: ShangHai Ji Ai Genetics & IVF Institute
• Contact: CAIXIA LEI, MD
• Phone: 86-18917958213
• Email: green3318[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

50%-60% of the known causes of recurrent pregnancy loss(RPL) are associated with embryonic aneuploidy, such that preimplantation genetic screening (PGS) on embryos acquired by assisted reproductive treatment should improve the rate of pregnancy and live birth in those patients. In dispute though the clinical application of PGS has been, a series of studies show that the new generation of PGS(PGS 2.0), based on blastocyst biopsy followed by whole genome analysis, has significantly improved the clinical outcome of IVF treatment. At present, there is still a need for the evidence of the use of PGS 2.0 in RPL patients, who may benefit from this emerging technology considering the prevalence of genetic abnormalities and the number of transferable embryos in this population.

An earlier single center RCT conducted by our IVF center displayed higher implantation rate, clinical pregnancy rate and ongoing pregnancy rate calculated by per embryo transfer(ET) cycle in IVF/ICSI+PGS group compared with IVF/ICSI group.

This multi-center prospective randomized clinical trial is to provide more data to determine whether the clinical outcomes are significantly improved per treatment cycle such that provide evidence for the application of PGS in RPL patients. Besides, risk factors of PGS outcome are to be analyzed from multi-center data to build a model for prediction of the possible outcomes of PGS and direction of the clinical choice.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 710
• Est. completion date: September 30, 2021
• Est. primary completion date: September 30, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 37 Years

Eligibility

Inclusion criteria:

1. The couple has experienced two or more failed pregnancies (according to ASRM definition).

2. The karyotypes of both husband and wife are normal (polymorphic chromosomes are considered normal either).

3. Women ages =20 and <38 years old.

Exclusion criteria:

1. the wife has history of the following diseases: a, the history of thyroid disease; b, the history of adrenal diseases; c, the history of sexually transmitted diseases; d, the history of hereditary diseases; e, the history of mental and psychological disorders.

2. the wife has the following uterine abnormalities: a, uterine malformations (uterus unicorns and duplex uterus), untreated septate uterus, adenomyoma, submucous uterine fibroids, endometrial polyps, or intrauterine adhesions (including the history of intrauterine adhesions).

3. the wife has a medical condition that contraindicate ART or pregnancy, including poorly controlled type I or type II diabetes; undiagnosed liver and renal disease or liver and renal insufficiency (based on blood test); deep vein thrombosis; pulmonary embolism; history of cerebrovascular accident; uncontrolled hypertension; cardiac disease; carcinoma; severe anemia; suspicious or undiagnosed vaginal bleeding.

Related Conditions & MeSH terms

• Abortion, Habitual
• Abortion, Spontaneous
• Fetal Death
• Infertility
• Infertility, Female
• Recurrent Pregnancy Loss

Intervention

Procedure:
• IVF/ICSI
in vitro fertilization or intracytoplasmatic sperm injection

Genetic:
• PGS 2.0
Blastocysts are selected by PGS 2.0(NGS based) and only euploid embryos will be transferred.

Other:
• Conventional embryo morphology evaluation
Blastocysts are selected by morphology criteria and only good-scored embryo will be transferred.

Locations

Country	Name	City	State
China	Shanghai Ji Ai Genetics & IVF Institute, Obstetrics and Gynecology Hospital, Fudan University	Shanghai	Shanghai

Sponsors (3)

Lead Sponsor	Collaborator
ShangHai Ji Ai Genetics & IVF Institute	Renji Hospital, Shanghai Jiao Tong University School of Medicine, The International Peace Maternity & Child Health Hospital of China welfare institute

Country where clinical trial is conducted

China, 

References & Publications (8)

Dahdouh EM, Balayla J, García-Velasco JA. Comprehensive chromosome screening improves embryo selection: a meta-analysis. Fertil Steril. 2015 Dec;104(6):1503-12. doi: 10.1016/j.fertnstert.2015.08.038. Epub 2015 Sep 16. Review. — View Citation

Dahdouh EM, Balayla J, García-Velasco JA. Impact of blastocyst biopsy and comprehensive chromosome screening technology on preimplantation genetic screening: a systematic review of randomized controlled trials. Reprod Biomed Online. 2015 Mar;30(3):281-9. doi: 10.1016/j.rbmo.2014.11.015. Epub 2014 Dec 11. Review. — View Citation

Forman EJ, Hong KH, Ferry KM, Tao X, Taylor D, Levy B, Treff NR, Scott RT Jr. In vitro fertilization with single euploid blastocyst transfer: a randomized controlled trial. Fertil Steril. 2013 Jul;100(1):100-7.e1. doi: 10.1016/j.fertnstert.2013.02.056. Epub 2013 Mar 30. — View Citation

Hodes-Wertz B, Grifo J, Ghadir S, Kaplan B, Laskin CA, Glassner M, Munné S. Idiopathic recurrent miscarriage is caused mostly by aneuploid embryos. Fertil Steril. 2012 Sep;98(3):675-80. doi: 10.1016/j.fertnstert.2012.05.025. Epub 2012 Jun 7. — View Citation

Kolte AM, Bernardi LA, Christiansen OB, Quenby S, Farquharson RG, Goddijn M, Stephenson MD; ESHRE Special Interest Group, Early Pregnancy. Terminology for pregnancy loss prior to viability: a consensus statement from the ESHRE early pregnancy special interest group. Hum Reprod. 2015 Mar;30(3):495-8. doi: 10.1093/humrep/deu299. Epub 2014 Nov 5. Review. — View Citation

Practice Committee of American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss: a committee opinion. Fertil Steril. 2013 Jan;99(1):63. doi: 10.1016/j.fertnstert.2012.09.023. Epub 2012 Oct 22. — View Citation

Scott RT Jr, Upham KM, Forman EJ, Hong KH, Scott KL, Taylor D, Tao X, Treff NR. Blastocyst biopsy with comprehensive chromosome screening and fresh embryo transfer significantly increases in vitro fertilization implantation and delivery rates: a randomized controlled trial. Fertil Steril. 2013 Sep;100(3):697-703. doi: 10.1016/j.fertnstert.2013.04.035. Epub 2013 Jun 1. — View Citation

Sermon K, Capalbo A, Cohen J, Coonen E, De Rycke M, De Vos A, Delhanty J, Fiorentino F, Gleicher N, Griesinger G, Grifo J, Handyside A, Harper J, Kokkali G, Mastenbroek S, Meldrum D, Meseguer M, Montag M, Munné S, Rienzi L, Rubio C, Scott K, Scott R, Simon C, Swain J, Treff N, Ubaldi F, Vassena R, Vermeesch JR, Verpoest W, Wells D, Geraedts J. The why, the how and the when of PGS 2.0: current practices and expert opinions of fertility specialists, molecular biologists, and embryologists. Mol Hum Reprod. 2016 Aug;22(8):845-57. doi: 10.1093/molehr/gaw034. Epub 2016 Jun 2. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Live birth rate per initiated cycle	live birth rate of a baby per oocyte retrieval cycle initiated	up to 42 days of a live birth
Secondary	Embryo implantation	positive serum hCG after 2 weeks of embryo transfer	2 weeks after embryo transfer
Secondary	Clinical pregnancy	the presence of a gestational sac confirmed by transvaginal ultrasound examination	4 weeks after embryo transfer
Secondary	Ongoing pregnancy	the fetal heat beat continued at 10 weeks after embryo transfer	10 weeks after embryo transfer
Secondary	Time to pregnancy	From the day of entering oocyte retrieval cycle to the embryo transfer day of a later assured ongoing pregnancy,which is up to 24 months within the study period.If the patient fails to obtain ongoing pregnancy during the study period, this outcome measure will not be recorded.	From the day of entering oocyte retrieval cycle to the embryo transfer day of a later assured ongoing pregnancy,which is up to 24 months within the study period.
Secondary	Pregnancy outcome	abortion, multiple birth, birth defects, preterm delivery, small for gestational age, still birth	up to 42 days of a live birth