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Pregnancy OutcomeNCT05457335

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

An observational study of Pregnancy Outcome and Time-to-Pregnancy, run by Shanghai First Maternity and Infant Hospital at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 20 to 45 years
Conditions the study is for
Pregnancy Outcome, Time-to-Pregnancy
What is being tested?
undergoing PGT
Type of treatment
Surgery or procedure
How many people
280 participants
Where
1 siteChina
Study dates
15 Jul 2022to 15 Jul 2024
How long will I take part?
12 Months
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 to 45 years
  • All sexes
  • No healthy volunteers
  • Adult

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.

Who may be able to join

  • 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.

Who cannot join

  • 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)

Trial locations and contacts

1 site in 1 country.

China1 site
  • Shanghai first Maternity and Infant health hospital, Tong Ji University

    Shanghai, 200051

    Zhi Qin Chen, Master, 86-21-54035206 ext. 2012, ptchen1@hotmail.com

    Hong chen, Master, 86-21-54035206 ext. 2012, charrychin@51mch.com

Other trials in China

About this study

Official title: Shanghai First Maternity and Infant Hospital,

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.

Read the 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.

Being tested
undergoing PGT
Keywords
preimplantation genetic testing, expectant management, live birth rate

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • undergoing PGTProcedure or surgery

    Preimplantation genetic testing for aneuploidy

Study groups in NCT05457335
Study groupRoleWhat they receive
PGT-A groupFor 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.
Receives: Procedure: undergoing PGT
Expectant management groupIn 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.
Receives: Procedure: undergoing PGT

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. cumulative live birth rate leading to live birth

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

    Measured: 12 Months

  2. time to live birth (TTLB).

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

    Measured: 24 Months

Secondary outcomes (7)
  1. Euploidy rate of blastocysts

    the number of euploid embryos divided by the total number of blastocysts

    Measured: 30 days

  2. Miscarriage rate

    the number of miscarriages before 22 weeks per pregnancy

    Measured: 3 months

  3. Number of oocytes retrieved

    oocytes retrieved per patient

    Measured: 14 days

  4. Cycle Cancellation rate

    number of PGT cycle with no viable embryo to transfer divided by number of PGT cycle initiated

    Measured: 28 days

  5. Clinical pregnancy per transfer /per PGTcycle/per attempt for natural conception

    presence of intrauterine gestational sac on ultrasound

    Measured: 28 days

  6. Implantation rate

    number of gestational sacs per embryo transferred

    Measured: 28 days

  7. on-going pregnancy per transfer /per PGTcycle/per attempt

    viable pregnancy beyond gestation 8 weeks

    Measured: 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jul 2022
  2. Study start15 Jul 2022 (estimated)
  3. Primary completion15 Jul 2023 (estimated)
  4. Study completion15 Jul 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
280 participants (estimated)
Target duration
12 Months
IDs, dates and publications
ClinicalTrials.gov ID
NCT05457335
Sponsor's protocol ID
shanghai first maternity
Status last verified
Jul 2022
First submitted
11 Jul 2022
Last updated
14 Jul 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 10548638
  • 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.

    PubMed 23548942
  • 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.

    PubMed 23367735
  • 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.

    PubMed 19643401
  • 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.

    PubMed 25772770
  • 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.

    PubMed 28620510
  • 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.

    PubMed 25681844
  • Stephenson MD. Frequency of factors associated with habitual abortion in 197 couples. Fertil Steril. 1996 Jul;66(1):24-9.

    PubMed 8752606
  • 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

  • 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

  • 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.

    PubMed 23780398

Questions about this trial

What is this clinical trial studying?

An observational study of Pregnancy Outcome and Time-to-Pregnancy, run by Shanghai First Maternity and Infant Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 14 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Zhi Qin Chen, MD (86-21-540355206 ext. 2078, ptchen1@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

cumulative live birth rate leading to live birth (time frame: 12 Months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05457335, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2022.

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