Impact of Caesarean section on pregnancy outcomes in ART after transfer of one or more frozen blastocysts

The prevalence of caesarean sections in France and worldwide is on the rise [1]. In the United States, a third of all births are by caesarean section [2]. In France, nearly one woman in five gives birth by caesarean section, and almost 50% of these are planned [3]. This is all the more true in assisted reproduction where, according to a meta-analysis, the incidence of caesarean section is multiplied by 1.9 compared to spontaneous conception [3]. This may be due to the older age of the patients, but also to an increase in obstetric complications (pre-eclampsia, placentation abnormalities) in this population [4,5]. In addition, the vision of the "precious pregnancy" held by both the couple and the practitioner is a factor that can influence the choice of delivery route [6]. In several countries, recourse to assisted reproduction technology (ART) and its associated healthcare costs are not covered by the healthcare system, but remain the responsibility of the couple. The use of ART is directly linked to affordability. In countries where costs are covered by the healthcare system, the number of new cycles per million women of childbearing age is higher than in countries without financial support (around 3,500 in France, compared with less than 500 in Brazil) [7]. This restricted access accentuates the "precious" nature of pregnancy when it does occur.

Two very powerful studies have demonstrated a reduction in fertility after Caesarean delivery [8,9]. The first, led by Murphy et al. in the UK, analyzed 14541 pregnancies, and found a more frequent delay in conception of more than a year after Caesarean section. The second, as early as 1985 by Hemminki et al. in the United States, showed greater difficulty in conceiving in this population. Kjerulff et al. conducted a prospective study in 2020 with a 3-year follow-up, revealing that women whose first delivery was by Caesarean section were less likely to conceive after unprotected intercourse [10]. One meta-analysis found a 9% lower chance of pregnancy and an 11% lower chance of achieving a live birth after Caesarean section [11]. In the context of ART, a meta-analysis carried out in China by Zhao et al. revealed a 16% drop in pregnancy rates and a 20% drop in live birth rates, as well as a 39% increase in miscarriages and an 8-fold increase in difficult transfers [12]. The authors suggest that the possible mechanisms affecting outcomes are the quality of the endometrium at the Caesarean scar, with potential destruction of the junction zone at this site.

The reduction in the number of vessels along the scar, could lead to hence delayed endometrial maturation [13]. Scarring may also impair myometrial contraction and endometrial decidualization [14]. Furthermore, the presence of an isthmocele would appear to promote fluid accumulation, leading to local inflammatory phenomena [15,16,17].

Like the prevalence of caesarean section, the use of frozen embryos has increased considerably with the development of embryo vitrification [18]. Given the increasing use of freezing, the cumulative live birth-rate (the result of fresh and frozen transfers on the same stimulation cycle) is a measure increasingly used to assess ART outcomes. So, some authors have taken an interest in the use of a single stimulation cycle with the "one-and-done" approach, which would enable two or more births to be obtained in almost a quarter of patients, whilst avoiding further oocyte retrievals [19].

Currently, when the situation allows it, blastocyst transfer is preferred as the chances of implantation are greater than those of an embryo at an earlier stage of development [20,21]. Nevertheless, current studies aimed at analyzing the effect of a scarred uterus on the chances of pregnancy in ART include all types of embryo (cleaved stage and prolonged culture), representing a significant bias given the differences in terms of the clinical pregnancy rate depending on the type of embryo used [22]. So far, no studies have ever included embryos derived solely from extended culture.

The aim of this study was to evaluate the impact of uterus scar pregnancy compared with a previous history of vaginal delivery, on the chances of live birth in assisted reproduction technology after the transfer of one or more frozen embryos at the blastocyst stage.

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