Impact of a Previous CS on the Ongoing Pregnancy Rate in Single Euploid Frozen Embryo Transfer (ET)

NCT ID: NCT05798624

Last Updated: 2024-07-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

1050 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-05-01

Study Completion Date

2025-07-30

Brief Summary

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As embryo ploidy is a crucial factor not only for implantation but also for maintenance of a pregnancy, the aim of this study is to evaluate the impact of the CS / isthmocele on the ongoing pregnancy rates and the implantation site in single euploid frozen embryo transfer, independent of the endometrial preparation approach.

Detailed Description

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The impact of a previous CS on the future fertility in the general population is discussed controversially, but it seems that the clinical and social circumstances leading to the CS have a greater effect on future fertility than the surgical procedure itself (Gurol-Urganci et al., 2013, 2014; Evers et al., 2014). However, this might be different in women who do not conceive spontaneously after a previous CS and need to undergo ART due to secondary infertility. Whereas some studies describe a reduction of implantation, ongoing pregnancy, and live birth (LB) rates (Vissers et al., 2020; Wang et al., 2020; Diao et al., 2021; Friedenthal et al., 2021; van den Tweel et al., 2022), others describe a negative impact of a previous CS only in the presence of an isthmocele (Diao et al., 2021) or no impact (Patounakis et al., 2016).

A case control study evaluated whether there are any differences in the location and distance to the internal cervical ostium of the implantation site of the intrauterine gestation sacs, early pregnancy symptoms and pregnancy outcome at 12 weeks gestation between women with and without a previous Caesarean section (CS) in patients who conceived naturally (Naji et al., 2013). Investigators concluded that the presence of a CS scar affects the site of implantation, and also that the distance between implantation site and the scar is related to the risk of spontaneous abortion.

This is a purely observational study without any intervention. Participants will be stratified into different groups according to their previous obstetrical history. Total sample size will include 1050 participants undergoing a frozen embryo transfer (FET) cycle.

Isthmocele will be defined according to de Vaate et al (Bij de Vaate et al., 2011) as: visible anechogenic area of at least 1 mm depth at the site of the Cesarean scar.

Conditions

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Infertility Implantation

Study Design

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Observational Model Type

OTHER

Study Time Perspective

PROSPECTIVE

Study Groups

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One CS with isthmocele

Ultrasound between 6+0 and 6+7 weeks of pregnancy - With Isthmocele

Intervention Type DIAGNOSTIC_TEST

Location of implantation of the GS (gestational sac) amended to Naji et al, defined as 3 possible implantation sites: (A: fundal, B: anterior, C: posterior)

Size of isthmocele:

* Depth of isthmocele
* Width of isthmocele
* Circumference of isthmocele

Distance between isthmocele and outer cervical os (measured with the trace line) Distance between CS scar and outer cervical os (measured with the trace line) Size of gestational sac Measurements of the isthmocele size / circumference / distance between isthmocele / CS and outer cervical os

More than one CS with Isthmocele

Ultrasound between 6+0 and 6+7 weeks of pregnancy - With Isthmocele

Intervention Type DIAGNOSTIC_TEST

Location of implantation of the GS (gestational sac) amended to Naji et al, defined as 3 possible implantation sites: (A: fundal, B: anterior, C: posterior)

Size of isthmocele:

* Depth of isthmocele
* Width of isthmocele
* Circumference of isthmocele

Distance between isthmocele and outer cervical os (measured with the trace line) Distance between CS scar and outer cervical os (measured with the trace line) Size of gestational sac Measurements of the isthmocele size / circumference / distance between isthmocele / CS and outer cervical os

One or more CS without isthmocele

Ultrasound between 6+0 and 6+7 weeks of pregnancy - Without Isthmocele

Intervention Type DIAGNOSTIC_TEST

Location of implantation of the GS amended to Naji et al, defined as 3 possible implantation sites: (A: fundal, B: anterior, C: posterior) Distance between CS scar and outer cervical os (measured with the trace line) Size of gestational sac

With previous vaginal delivery

Ultrasound between 6+0 and 6+7 weeks of pregnancy

Intervention Type DIAGNOSTIC_TEST

Location of implantation of the GS (gestational sac) amended to Naji et al, defined as 3 possible implantation sites (A: fundal, B: anterior, C: posterior)

Size of gestational sac

With first ongoing pregnancy

Ultrasound between 6+0 and 6+7 weeks of pregnancy

Intervention Type DIAGNOSTIC_TEST

Location of implantation of the GS (gestational sac) amended to Naji et al, defined as 3 possible implantation sites (A: fundal, B: anterior, C: posterior)

Size of gestational sac

Interventions

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Ultrasound between 6+0 and 6+7 weeks of pregnancy - With Isthmocele

Location of implantation of the GS (gestational sac) amended to Naji et al, defined as 3 possible implantation sites: (A: fundal, B: anterior, C: posterior)

Size of isthmocele:

* Depth of isthmocele
* Width of isthmocele
* Circumference of isthmocele

Distance between isthmocele and outer cervical os (measured with the trace line) Distance between CS scar and outer cervical os (measured with the trace line) Size of gestational sac Measurements of the isthmocele size / circumference / distance between isthmocele / CS and outer cervical os

Intervention Type DIAGNOSTIC_TEST

Ultrasound between 6+0 and 6+7 weeks of pregnancy - Without Isthmocele

Location of implantation of the GS amended to Naji et al, defined as 3 possible implantation sites: (A: fundal, B: anterior, C: posterior) Distance between CS scar and outer cervical os (measured with the trace line) Size of gestational sac

Intervention Type DIAGNOSTIC_TEST

Ultrasound between 6+0 and 6+7 weeks of pregnancy

Location of implantation of the GS (gestational sac) amended to Naji et al, defined as 3 possible implantation sites (A: fundal, B: anterior, C: posterior)

Size of gestational sac

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

\- All participants undergoing a single euploid FET, independent of the endometrial preparation approach

Exclusion Criteria

* Intracavitary fluid during preparation for FET
* Known anomaly of the uterus or the adnexae (e.g.: fibroids, polyps, hydrosalpinx, endometriosis, adenomyosis)
* Embryo which was biopsied on day 7
* Poor quality embryo which was transferred (Gardner criteria: AC / BC / CB, biopsied on day 6 and CC embryos from both, day 5 and day 6 biopsies, classified as "poor" quality embryos)
* History of recurrent abortion
* Antiphospholipid syndrome / autoimmune diseases
Minimum Eligible Age

18 Years

Maximum Eligible Age

42 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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ART Fertility Clinics LLC

OTHER

Sponsor Role lead

Responsible Party

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Barbara Lawrenz

Scientific Director

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Barbara Lawrenz, PhD

Role: PRINCIPAL_INVESTIGATOR

ART Fertility Clinics LLC

Locations

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ART Fertility Clinics LLC

Abu Dhabi, , United Arab Emirates

Site Status RECRUITING

Countries

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United Arab Emirates

Central Contacts

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Barbara Lawrenz, PhD

Role: CONTACT

+971 2 652 8000 ext. 1108

Jonalyn Edades

Role: CONTACT

+971 2 652 8000 ext. 1106

Facility Contacts

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Barbara Lawrenz, PhD

Role: primary

+971 2 652 8000 ext. 1108

Jonalyn Edades

Role: backup

+971 2 652 8000 ext. 1106

References

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Betran AP, Ye J, Moller AB, Souza JP, Zhang J. Trends and projections of caesarean section rates: global and regional estimates. BMJ Glob Health. 2021 Jun;6(6):e005671. doi: 10.1136/bmjgh-2021-005671.

Reference Type BACKGROUND
PMID: 34130991 (View on PubMed)

Bij de Vaate AJ, Brolmann HA, van der Voet LF, van der Slikke JW, Veersema S, Huirne JA. Ultrasound evaluation of the Cesarean scar: relation between a niche and postmenstrual spotting. Ultrasound Obstet Gynecol. 2011 Jan;37(1):93-9. doi: 10.1002/uog.8864.

Reference Type BACKGROUND
PMID: 21031351 (View on PubMed)

Diao J, Gao G, Zhang Y, Wang X, Zhang Y, Han Y, Du A, Luo H. Caesarean section defects may affect pregnancy outcomes after in vitro fertilization-embryo transfer: a retrospective study. BMC Pregnancy Childbirth. 2021 Jul 6;21(1):487. doi: 10.1186/s12884-021-03955-7.

Reference Type BACKGROUND
PMID: 34229640 (View on PubMed)

Evers EC, McDermott KC, Blomquist JL, Handa VL. Mode of delivery and subsequent fertility. Hum Reprod. 2014 Nov;29(11):2569-74. doi: 10.1093/humrep/deu197. Epub 2014 Aug 27.

Reference Type BACKGROUND
PMID: 25164023 (View on PubMed)

Friedenthal J, Alkon-Meadows T, Hernandez-Nieto C, Gounko D, Lee JA, Copperman A, Buyuk E. The association between prior cesarean delivery and subsequent in vitro fertilization outcomes in women undergoing autologous, frozen-thawed single euploid embryo transfer. Am J Obstet Gynecol. 2021 Sep;225(3):287.e1-287.e8. doi: 10.1016/j.ajog.2021.03.026. Epub 2021 Mar 30.

Reference Type BACKGROUND
PMID: 33798478 (View on PubMed)

Gurol-Urganci I, Bou-Antoun S, Lim CP, Cromwell DA, Mahmood TA, Templeton A, van der Meulen JH. Impact of Caesarean section on subsequent fertility: a systematic review and meta-analysis. Hum Reprod. 2013 Jul;28(7):1943-52. doi: 10.1093/humrep/det130. Epub 2013 May 3.

Reference Type BACKGROUND
PMID: 23644593 (View on PubMed)

Gurol-Urganci I, Cromwell DA, Mahmood TA, van der Meulen JH, Templeton A. A population-based cohort study of the effect of Caesarean section on subsequent fertility. Hum Reprod. 2014 Jun;29(6):1320-6. doi: 10.1093/humrep/deu057. Epub 2014 Apr 29.

Reference Type BACKGROUND
PMID: 24781430 (View on PubMed)

Lawrenz B, Melado L, Garrido N, Coughlan C, Markova D, Fatemi H. Isthmocele and ovarian stimulation for IVF: considerations for a reproductive medicine specialist. Hum Reprod. 2020 Jan 1;35(1):89-99. doi: 10.1093/humrep/dez241.

Reference Type BACKGROUND
PMID: 31885047 (View on PubMed)

Naji O, Wynants L, Smith A, Abdallah Y, Saso S, Stalder C, Van Huffel S, Ghaem-Maghami S, Van Calster B, Timmerman D, Bourne T. Does the presence of a Caesarean section scar affect implantation site and early pregnancy outcome in women attending an early pregnancy assessment unit? Hum Reprod. 2013 Jun;28(6):1489-96. doi: 10.1093/humrep/det110. Epub 2013 Apr 12.

Reference Type BACKGROUND
PMID: 23585560 (View on PubMed)

Patounakis G, Ozcan MC, Chason RJ, Norian JM, Payson M, DeCherney AH, Yauger BJ. Impact of a prior cesarean delivery on embryo transfer: a prospective study. Fertil Steril. 2016 Aug;106(2):311-6. doi: 10.1016/j.fertnstert.2016.03.045. Epub 2016 Apr 14.

Reference Type BACKGROUND
PMID: 27087400 (View on PubMed)

Sandall J, Tribe RM, Avery L, Mola G, Visser GH, Homer CS, Gibbons D, Kelly NM, Kennedy HP, Kidanto H, Taylor P, Temmerman M. Short-term and long-term effects of caesarean section on the health of women and children. Lancet. 2018 Oct 13;392(10155):1349-1357. doi: 10.1016/S0140-6736(18)31930-5.

Reference Type BACKGROUND
PMID: 30322585 (View on PubMed)

van den Tweel MM, Klijn NF, Diaz de Pool JDN, van der Westerlaken LAJ, Louwe LA. Previous caesarean section is associated with lower subsequent in vitro fertilization live birth rates. Hum Fertil (Camb). 2022 Feb;25(1):93-98. doi: 10.1080/14647273.2019.1696990. Epub 2019 Dec 3.

Reference Type BACKGROUND
PMID: 31793367 (View on PubMed)

Vissers J, Sluckin TC, van Driel-Delprat CCR, Schats R, Groot CJM, Lambalk CB, Twisk JWR, Huirne JAF. Reduced pregnancy and live birth rates after in vitro fertilization in women with previous Caesarean section: a retrospective cohort study. Hum Reprod. 2020 Mar 27;35(3):595-604. doi: 10.1093/humrep/dez295.

Reference Type BACKGROUND
PMID: 32142117 (View on PubMed)

Wang L, Yao W, Tang X, Yao H, Wei S, Huang J, Mol BWJ, Jin L, Yue J, Wang R. Fertility outcomes of IVF/ICSI after Caesarean section: a cohort study. Reprod Biomed Online. 2020 May;40(5):719-728. doi: 10.1016/j.rbmo.2019.12.004. Epub 2019 Dec 16.

Reference Type BACKGROUND
PMID: 32336649 (View on PubMed)

Other Identifiers

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2303-ABU-003-BL

Identifier Type: -

Identifier Source: org_study_id

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