Isthmocele and ovarian stimulation for IVF: considerations for a reproductive medicine specialist

Abstract

STUDY QUESTION What is the risk of developing intracavitary fluid (ICF) during ovarian stimulation in patients with an isthmocele after previous caesarean section (CS) delivery? SUMMARY ANSWER In patients with an existing isthmocele, the risk of developing ICF during hormonal stimulation for IVF is almost 40%; therefore, special attention has to be paid to exclude fluid accumulation during stimulation and particularly at the time of transfer, in which case the reproductive outcomes of frozen embryo transfer (FET) cycles appear to be uncompromised. WHAT IS KNOWN ALREADY Lately, there is an increasing focus on the long-term impact of CS delivery on the health and future fertility of the mother. Development of an isthmocele is one of the sequelae of a CS delivery. The presence of ICF in combination with an isthmocele has been described previously, and the adverse effect of endometrial fluid on implantation is well recognised by reproductive medicine specialists. Accumulation of ICF has been previously described in patients with hydrosalpinx, less commonly in patients with polycystic ovary syndrome undergoing ovarian stimulation for IVF/ICSI, and even in some patients without any identifiable reason. Assisted reproductive techniques (ARTs) are a means to overcome infertility. Reproductive medicine specialists commonly see patients with secondary infertility with a history of having had one or more previous CS and with ultrasound confirmation of an isthmocele. However, the available data pertaining to the prevalence of intracavitary fluid during ovarian stimulation in patients with ultrasound confirmation of an isthmocele is limited. Furthermore, data on the influence of ICF in a stimulated cycle on the ART outcome of a subsequent FET cycle is scarce and merits further studies. STUDY DESIGN, SIZE, DURATION A prospective observational exploratory study was performed in IVI Middle East Fertility Clinic, Abu Dhabi, from June 2018 to March 2019, and retrospective analysis of the reproductive outcomes was performed until July 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients with secondary infertility, defined as a minimum of 1 year of infertility after a previous successful pregnancy, undergoing ovarian stimulation for IVF/ICSI and having a history of one or more previous CS with ultrasonographic visible isthmocele, were included (n = 103). Patients were monitored as a clinical routine with vaginal ultrasound examinations during ovarian stimulation for IVF/ICSI treatment. All patients included in the study were asked to complete a questionnaire regarding their previous obstetric history. Development of ICF was recorded as well as changes in the measurements of the isthmocele during the course of ovarian stimulation. Reproductive outcomes of FET cycles of the patients with an isthmocele were retrospectively compared to those of patients with infertility and without isthmocele in our clinic during the same time period. MAIN RESULTS AND THE ROLE OF CHANCE Patients with an existing isthmocele after previous CS have a risk of ~40% of developing ultrasonographic visible fluid in the endometrial cavity during the course of ovarian stimulation. Development of ICF was significantly correlated with the depth of the isthmocele on Day 2/3 (P = 0.038) and on the day of trigger (−1/−2 days) (P = 0.049), circumference of the isthmocele on the day of trigger (−1/−2 days) (P = 0.040), distance from the C-scar to the external os (P = 0.036), number of children delivered (P = 0.047) and number of previous CS (P = 0.035). There was a statistically significant increase in the parameters related to the size of the isthmocele during ovarian stimulation. No significant differences in the reproductive outcome (pregnancy rate and rates of biochemical and ectopic pregnancies, miscarriages and ongoing/delivered pregnancies) after FET were found between the patients with and without an isthmocele, when ICF was excluded prior to embryo transfer procedure. LARGE-SCALE DATA NA. LIMITATIONS, REASONS FOR CAUTION This study was not primarily designed to investigate the causes of ICF during ovarian stimulation or to evaluate the reproductive outcomes. Further, the small number of reported reproductive outcomes may be seen as a limitation. WIDER IMPLICATIONS OF THE FINDINGS The data highlights the need for an increased awareness on the part of reproductive medicine specialists towards the potentially adverse impact of an isthmocele on ART treatment, as there is a potential to develop intracavitary fluid during ovarian stimulation for IVF. The increase in the circumference of the isthmocele may increase embryo transfer difficulty. STUDY FUNDING/COMPETING INTEREST(S) No funding of the study has to be reported. The authors have no competing interests. TRIAL REGISTRATION NUMBER This prospective study was registered with clinicaltrials.gov. under the number NCT03518385.

Intra-Cavitary Fluid Resulted From Caesarean Section But Not Isthmocele Compromised Clinical Pregnancy After IVF/ICSI Treatment

“…Moreover, the reported incidence of ICF may reach 40% [7]. We hypothesize that the presence of ICF may play an important role in reducing the endometrium receptivity and may further affect pregnancy outcomes.…”

“…Vissers et al [29] also reported an impact on clinical pregnancy and implantation of CS, but they did not perform further analysis of the scar and its associated effects. In the recent study by Lawrenz et al [7], an association between ICF and uncompromised clinical outcomes was mentioned, and the researchers conducted a detailed analysis of the possible factors of the production of effusion. Another study concluded that a subgroup of patients with symptomatic isthmocele may bene t from hysteroscopic isthmoplasty, which can help con rm the effect of ICF on pregnancy from another perspective [30].…”

“…With the increasing CS rate worldwide, more infertile women are seeking to become pregnant with a scar on their uterus. Many studies have con rmed an uncompromised clinical outcome in patients with a history of CS and reported an even lower pregnancy rate when a niche was mentioned [7,24,30,32,33]. Previous studies agere that there is an impact in clinical outcomes, though some of them focus on isthmocele, and they describe blood or mucus on catheter [34].…”

“…Previous research has been directed towards the impact of the CS scar and the isthmocele. Prior research has examined the association of isthmocele and pregnancy outcome among patients undergoing IVF [7].…”

“…It was reported that the existence of a CS scar may impact embryo implantation and clinical pregnancy outcome compared to vaginal delivery (VD) in a retrospective study [9]. Lawrenz et al also reported the relationship between ICF and uncompromised clinical outcomes on frozen embryo transfer (FET) cycles, which were unaffected when ICF cases were excluded [7]. The potential causes of the lower pregnancy rates in patients with a history of CS still remain to be investigated.…”