Clinical trial NCT05798624: Impact of a Previous CS on the Ongoing Pregnancy Rate in Single Euploid Frozen Embryo Transfer (ET)
Official title: To Study the Impact of a Previous Cesarean Section (CS) With / Without an Isthmocele on the Ongoing Pregnancy Rate in Single Euploid Frozen Embryo Transfer
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Infertility
Implantation
Keywords: Implantation
Infertility
Isthmocele
Cesarean section
Lead sponsor: ART Fertility Clinics LLC
Sponsor class: OTHER
First posted: 2023-04-04
Enrollment: 1050
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 42
Standard ages: ADULT
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Female undergoing IVF/ICSI treatment

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Ongoing pregnancy rate
timeFrame: 5 weeks
measure: Implantation rate
timeFrame: 6 weeks
measure: Implantation site
timeFrame: 6 weeks
measure: Rate of vaginal bleeding in early pregnancy (until 12 weeks of gestation)
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Abu Dhabi
country: United Arab Emirates
facility: ART Fertility Clinics LLC
Study officials:
affiliation: ART Fertility Clinics LLC
name: Barbara Lawrenz, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.