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

NCT05457335 | Unknown

• 1 other identifier: shanghai first maternity
• Study Type: observational
• Target: 280
• Locations: 1 country
• Sites: 1

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.

Conditions

Pregnancy Outcome; Time-to-Pregnancy

Keywords

preimplantation genetic testing; expectant management; live birth rate

Outcome Measures

Primary Outcomes (2)

• cumulative live birth rate leading to live birth

  the ongoing status had to be achieved within 12 months since patient inclusion

  12 Months

• time to live birth (TTLB).

  TTLB was measured as the time from patient inclusion to a live birth.

  24 Months

Secondary Outcomes (7)

• Euploidy rate of blastocysts

  30 days

• Miscarriage rate

  3 months

• Number of oocytes retrieved

  14 days

• Cycle Cancellation rate

  28 days

• Clinical pregnancy per transfer /per PGTcycle/per attempt for natural conception

  28 days

Other Outcomes (1)

• adverse events

  2 years

Study Arms (2)

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.

Procedure: undergoing PGT

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.

Procedure: undergoing PGT

Interventions

undergoing PGT PROCEDURE

Preimplantation genetic testing for aneuploidy

Expectant management group; PGT-A group

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Infertile women who have medical indication attending the Assisted Reproduction clinic, Shanghai First Maternity and Infant Hospital for IVF will be recruited for study after explanation and counseling if they fulfill the inclusion criteria and do not have the exclusion criteria.

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Shanghai First Maternity and Infant Hospital: lead

Study Sites (1)

Shanghai first Maternity and Infant health hospital, Tong Ji University

Shanghai, 200051, China

Location

Related Publications (11)

• 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.

  PMID: 10548638 RESULT

• 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.

  PMID: 23548942 RESULT

• 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.

  PMID: 23367735 RESULT

• 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.

  PMID: 19643401 RESULT

• 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.

  PMID: 25772770 RESULT

• 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.

  PMID: 28620510 RESULT

• 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.

  PMID: 25681844 RESULT

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

  PMID: 8752606 RESULT

• 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

  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

  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.

  PMID: 23780398 RESULT

Study Officials

• Zhi Qin Chen, MD

  Shanghai first maternty and infant hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhi Qin Chen, MD

CONTACT

86-21-540355206; ptchen1@hotmail.com

Hong Chen, MD

CONTACT

86-21-540355206; 765230197@qq.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 12 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: clinical doctor in chief

Study Record Dates

• First Submitted: July 11, 2022
• First Posted: July 14, 2022
• Study Start: July 15, 2022
• Primary Completion: July 15, 2023
• Study Completion: July 15, 2024
• Last Updated: July 14, 2022

Record last verified: 2022-07

Locations

CN (1)