2.Comparison of the Live Birth Rate of PGT Versus Expectant Management in Patients With RPL

NCT ID: NCT05457335

Last Updated: 2022-07-14

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 280 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-07-15
• Study Completion Date: 2024-07-15

Brief Summary

Recurrent pregnancy loss (RPL) is a multifactorial disorder defined by the American Society for Reproductive Medicine (ASRM) as two or more clinical miscarriages (CMs). However, US guidelines differ with European guidelines which defined recurrent miscarriage as three consecutive prior pregnancy losses (The Royal College of Obstetricians and Gynaecologists Green-Top Guideline, 2011). Thus, there is currently no uniformly agreed upon definition of RPL, the ASRM recommends that a clinical evaluation for RPL commence following two early pregnancy losses, and that a threshold of three prior pregnancy losses be utilized for epidemiologic studies (The Practice Committee of the American Society for Reproductive Medicine, 2012).

Although the overall incidence of RPL is low and estimated at 5% of women (The Practice Committee of the American Society for Reproductive Medicine, 2012), it presents a significant diagnostic and treatment challenge for both patients and clinicians. Guidelines for the evaluation of patients with RPL include evaluation of the uterine cavity and blood work to determine parental karyotypes and the presence of anti-phospholipid antibodies (APLA). In at least 50% of patients, however, an etiology for RPL is not identified (Stirrat, 1990; Stephenson, 1996; Stephenson and Kutteh, 2007; The Practice Committee of the American Society for Reproductive Medicine, 2012). The ASRM recommends expectant management as the current standard of care for patients with unexplained RPL (The Practice Committee of the American Society for Reproductive Medicine, 2012). Counseling patients with unexplained RPL to pursue expectant management presents several challenges. Patients often feel an urgency to conceive and expectant management can feel like a passive and time-consuming approach to conception. In addition, patients often carry a significant amount of guilt and grief in association with miscarriage. Attempting spontaneous conception can feel emotionally vulnerable; Despite reassurance of good prognosis, patients doubt that a subsequent pregnancy will be successful (Lachmi-Epstein et al., 2012). For all of these reasons, IVF and preimplantation genetic testing (PGT) have been investigated as a treatment strategy in RPL patients with the goals of shortening time to pregnancy, decreasing CM rates and increasing live birth (LB) rates.

Detailed Description

The role of aneuploidy in CM is well known, with over 50% of pregnancy losses attributed to fetal chromosomal abnormalities (Viaggi et al., 2013). Furthermore, for patients greater than 35 years of age with RPL, fetal aneuploidy is responsible for up to 80% of first trimester losses (Marquard et al., 2010). Due to the prevalence of aneuploidy in first trimester losses and in the RPL population, PGT has been proposed as a method for reducing miscarriage by selecting only euploid embryos for transfer (Shahine and Lathi, 2014). The ultimate effect of PGT on increasing LB rates in the RPL population and the time interval to conception are areas of investigation. Current studies are largely retrospective in design with several limitations. For example: Inconsistent definitions of CM and RPL are employed. In addition, the treatment group (IVF and PGT) has been compared with a variety of control groups including IVF without PGT, a control infertile population, or to predicted LB and CM rates based on age and clinical history, but has not been compared with expectant management (Shahine and Lathi, 2014). Finally, the majority of studies report clinical outcomes only of patients who reach PGT biopsy and/or embryo transfer, so all possible cycle outcomes are not captured (Hodes-Wertz et al., 2012).

For the absence of well-designed prospective studies with high level of evidence comparing IVF and PGT to the current standard of care, expectant management, have been performed to date for the treatment of RPL patients. The objective of this study is to perform an intent to treat analysis comparing live birth rate of IVF and PGT to expectant management in fertile RPL patients in one year followed- up period.

Conditions

Pregnancy Outcome; Time-to-Pregnancy

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

PGT-A group

For patients undergoing PGT-A, trophectoderm biopsy was performed on good quality blastocysts and about five cells were aspirated gently and separated from the blastocyst by applying multiple pulses of a noncontact 1.48- μm diode laser (Saturn 5 ActiveTM, Cooper Surgical, Inc., CT, USA) through a zona pellucida opening created by the laser. The biopsied cells were washed three times in 1 × phosphate buffered saline (PBS) (Life Technologies, NY, USA), transferred to a PCR tube containing 2.5 μl 1× PBS and cryopreserved at -80◦C until analysis. Genetic laboratories analyzed and interpreted biopsies. The genetic screening was performed using the next-generation sequencing (NGS)-based assay VeriSeq PGS following standard protocols and manufacturer recommendations (Illumina Inc., San Diego, USA）. The PGT-A report can be euploid, aneuploidy, mosaic and non-conclusive. Euploid embryos were transferred while aneuploid and mosaic embryos were not replaced.

undergoing PGT

Intervention Type: PROCEDURE

Preimplantation genetic testing for aneuploidy

Expectant management group

In the this group, one attempt at conception was defined as one calendar months trying to conceive spontaneously. Either in natural cycles for ovulatory women and in clomiphene/letrozol induced cycles for anovulatory women with or without ultrasound monitoring.

undergoing PGT

Intervention Type: PROCEDURE

Preimplantation genetic testing for aneuploidy

Interventions

undergoing PGT

Preimplantation genetic testing for aneuploidy

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Age of women <45 years
• Two or more clinical miscarriages with identified foetal chromosomal abnormalities, or three consecutive prior pregnancy losses between 6 and 20 weeks gestational age, excluding biochemical pregnancies.

Exclusion Criteria

• Presence of APLA including anti-cardiolipin antibody, lupus anticoagulant and b-2-glycoprotein
• Diagnosis for hypothyroidism and hyperprolactinemia with uncontrolled serum thyroid-stimulating hormone and prolactin
• Having a anomaly uterine cavity
• Abormal parental karyotypes (translocation carriers and monogenetic defect)

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai First Maternity and Infant Hospital

OTHER

Sponsor Role: lead

Responsible Party

chen zhi qin

clinical doctor in chief

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhi Qin Chen, MD

Role: PRINCIPAL_INVESTIGATOR

Shanghai first maternty and infant hospital

Locations

Shanghai first Maternity and Infant health hospital, Tong Ji University

Shanghai, , China

Countries

China

Central Contacts

Zhi Qin Chen, MD

Role: CONTACT

ptchen1@hotmail.com

86-21-540355206 ext. 2078

Hong Chen, MD

Role: CONTACT

765230197@qq.com

86-21-540355206 ext. 2345

Facility Contacts

Zhi Qin Chen, Master

Role: primary

ptchen1@hotmail.com

86-21-54035206 ext. 2012

Hong chen, Master

Role: backup

charrychin@51mch.com

86-21-54035206 ext. 2012

References

Brigham SA, Conlon C, Farquharson RG. A longitudinal study of pregnancy outcome following idiopathic recurrent miscarriage. Hum Reprod. 1999 Nov;14(11):2868-71. doi: 10.1093/humrep/14.11.2868.

Reference Type: RESULT

PMID: 10548638 (View on PubMed)

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.

Reference Type: RESULT

PMID: 23548942 (View on PubMed)

Lachmi-Epstein A, Mazor M, Bashiri A. [Psychological and mental aspects and "tender loving care" among women with recurrent pregnancy losses]. Harefuah. 2012 Nov;151(11):633-7, 654. Hebrew.

Reference Type: RESULT

PMID: 23367735 (View on PubMed)

Marquard K, Westphal LM, Milki AA, Lathi RB. Etiology of recurrent pregnancy loss in women over the age of 35 years. Fertil Steril. 2010 Sep;94(4):1473-1477. doi: 10.1016/j.fertnstert.2009.06.041. Epub 2009 Jul 30.

Reference Type: RESULT

PMID: 19643401 (View on PubMed)

Murugappan G, Ohno MS, Lathi RB. Cost-effectiveness analysis of preimplantation genetic screening and in vitro fertilization versus expectant management in patients with unexplained recurrent pregnancy loss. Fertil Steril. 2015 May;103(5):1215-20. doi: 10.1016/j.fertnstert.2015.02.012. Epub 2015 Mar 13.

Reference Type: RESULT

PMID: 25772770 (View on PubMed)

Perfetto CO, Murugappan G, Lathi RB. Time to next pregnancy in spontaneous pregnancies versus treatment cycles in fertile patients with recurrent pregnancy loss. Fertil Res Pract. 2015 Apr 21;1:5. doi: 10.1186/2054-7099-1-5. eCollection 2015.

Reference Type: RESULT

PMID: 28620510 (View on PubMed)

Shahine L, Lathi R. Recurrent pregnancy loss: evaluation and treatment. Obstet Gynecol Clin North Am. 2015 Mar;42(1):117-34. doi: 10.1016/j.ogc.2014.10.002.

Reference Type: RESULT

PMID: 25681844 (View on PubMed)

Stephenson MD. Frequency of factors associated with habitual abortion in 197 couples. Fertil Steril. 1996 Jul;66(1):24-9.

Reference Type: RESULT

PMID: 8752606 (View on PubMed)

Stirrat GM. Recurrent miscarriage. Lancet 1990;336:673- 675. The PracticeCommittee of the American Society for ReproductiveMedicine. Evaluation and Treatment of Recurrent Pregnancy Loss: A Committee Opinion. Feril Steril 2012;98:1103 - 1111

Reference Type: RESULT

Regan L, Backos M, Rai R. The Royal College of Obstetricians and Gynaecologists. The RCOG Green-Top Guideline No. 17. The Investigation and Treatment of Couples with Recurrent First-trimester and Second-trimester Miscarriage. 2011

Reference Type: RESULT

Viaggi CD, Cavani S, Malacarne M, Floriddia F, Zerega G, Baldo C, Mogni M, Castagnetta M, Piombo G, Coviello DA, Camandona F, Lijoi D, Insegno W, Traversa M, Pierluigi M. First-trimester euploid miscarriages analysed by array-CGH. J Appl Genet. 2013 Aug;54(3):353-9. doi: 10.1007/s13353-013-0157-x. Epub 2013 Jun 19.

Reference Type: RESULT

PMID: 23780398 (View on PubMed)

Other Identifiers

shanghai first maternity

Identifier Type: -

Identifier Source: org_study_id