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

Pregnancy Outcome Clinical Trial

Official title:

Shanghai First Maternity and Infant Hospital,

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05457335
• Other study ID #: shanghai first maternity
• Status: Not yet recruiting
• Start date: July 15, 2022
• Est. completion date: July 15, 2024

Study information

• Verified date: July 2022
• Source: Shanghai First Maternity and Infant Hospital
• Contact: Zhi Qin Chen, MD
• Phone: 86-21-540355206
• Email: ptchen1[@]hotmail.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical 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 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 280
• Est. completion date: July 15, 2024
• Est. primary completion date: July 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 45 Years

Eligibility

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)

Related Conditions & MeSH terms

• Pregnancy Outcome

Intervention

Procedure:
• undergoing PGT
Preimplantation genetic testing for aneuploidy

Locations

Country	Name	City	State
China	Shanghai first Maternity and Infant health hospital, Tong Ji University	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai First Maternity and Infant Hospital

Country where clinical trial is conducted

China, 

References & 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. — 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. Ep — View Citation

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. Review. Hebrew. — View Citation

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. — View Citation

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 — View Citation

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. — View Citation

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

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. Review. — View Citation

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

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

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;5 — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	adverse events	: multiple pregnancy, ectopic pregnancy, ,pelvic infection, fetal or congenital defects, obstetric complications, birth weight of babies	2 years
Primary	cumulative live birth rate leading to live birth	the ongoing status had to be achieved within 12 months since patient inclusion	12 Months
Primary	time to live birth (TTLB).	TTLB was measured as the time from patient inclusion to a live birth.	24 Months
Secondary	Euploidy rate of blastocysts	the number of euploid embryos divided by the total number of blastocysts	30 days
Secondary	Miscarriage rate	the number of miscarriages before 22 weeks per pregnancy	3 months
Secondary	Number of oocytes retrieved	oocytes retrieved per patient	14 days
Secondary	Cycle Cancellation rate	number of PGT cycle with no viable embryo to transfer divided by number of PGT cycle initiated	28 days
Secondary	Clinical pregnancy per transfer /per PGTcycle/per attempt for natural conception	presence of intrauterine gestational sac on ultrasound	28 days
Secondary	Implantation rate	number of gestational sacs per embryo transferred	28 days
Secondary	on-going pregnancy per transfer /per PGTcycle/per attempt	viable pregnancy beyond gestation 8 weeks	3 months