Isthmocele : traiter ou attendre ? Le dilemme continue

Résumé libre de l'article publié dans Fertility & Sterility par Dominique de Ziegler (board scientifique de la Maison de la Fertilité), Anuja Dokras, Edgardo Somigliana, Olivier Donnez, Leigh A. Humphries, Divya K. Shah, Mindy S. Christianson.

Isthmocele : faut-il la réparer ou simplement surveiller ?

L’isthmocele, aussi appelée défaut de cicatrice de césarienne, est une petite cavité qui se forme à l’endroit de la cicatrice utérine après une césarienne. Elle est très fréquente (jusqu’à 80 % des femmes après un accouchement par césarienne), mais reste souvent asymptomatique.Chez certaines femmes, elle peut cependant provoquer des saignements après les règles, des douleurs pelviennes ou parfois une baisse de fertilité.

Pourquoi cela peut poser problème

L’isthmocele peut retenir du sang menstruel ou des sécrétions, entraînant une inflammation de la muqueuse utérine et perturbant le passage des spermatozoïdes ou la nidation de l’embryon. Certaines études montrent en effet une diminution du taux de réussite des FIV chez les femmes présentant une isthmocele.

Les arguments pour la chirurgie

Les partisans d’une approche active estiment qu’une correction chirurgicale (par hystéroscopie, laparoscopie ou voie vaginale) peut :

• soulager les symptômes (douleurs, saignements) dans plus de 80 % des cas,

• et améliorer la fertilité, notamment quand le myomètre restant est très fin (<3 mm).

Les techniques laparoscopiques, plus réparatrices, semblent restaurer une meilleure structure utérine et des taux de grossesse encourageants.

Les arguments pour la surveillance

D’autres spécialistes rappellent qu’il n’existe pas encore assez de preuves solides que la chirurgie améliore réellement les chances de grossesse.

• La majorité des femmes avec une isthmocele n’ont aucun symptôme ni problème de fertilité.

• Les études existantes sont souvent petites et peu comparatives.

• Dans certains cas, un simple traitement hormonal suffit à réduire les saignements.L’intervention chirurgicale est donc réservée aux patientes symptomatiques ou infertiles, après discussion personnalisée.

Les freins pratiques

Même si la chirurgie peut aider certaines femmes, sa diffusion reste limitée :

• absence de standardisation des techniques,

• manque de formation spécifique des chirurgiens,

• et difficultés de remboursement (le code médical dédié à l’isthmocele n’existe que depuis peu).

En résumé

L’isthmocele est un trouble fréquent mais souvent bénin. La chirurgie peut être utile chez certaines patientes souffrant de douleurs, de saignements persistants ou d’infertilité inexpliquée, mais elle n’est pas nécessaire pour toutes. L’essentiel est de personnaliser la prise en charge :surveiller quand c’est possible, opérer quand c’est justifié — toujours après une discussion éclairée entre la patiente et son médecin.

Texte Original en Anglais :

Isthmocele—fix it or observe, an ongoing dilemma

PRO: Isthmocele should be fixed surgically

Edgardo Somigliana, M.D., Ph.D.

The cesarean section (CS) is associated with subsequent infertility. According to the most recent meta-analysis, women delivering by cesarean have a 9% lower subsequent fertility (Relative Risk [RR] = 0.91, 95% confidence interval [CI]: 0.88–0.94) (1). The presence of cesarean scar defect (CSD) (also named isthmocele) may be one of the causes of this detrimental effect (2). This iatrogenic niche may retain menstrual blood debris or cervical secretions that could enter the endometrial cavity after the end of menses, interfering with the fine molecular equilibrium that allows embryo implantation. It may also perturb uterine peristalsis and interfere with sperm passage through the cervix and the isthmus.

A recent meta-analysis showed that the presence of a CSD is associated with a 38% reduction in the rate of success of Assisted Reproduction Technologies (ART) (odds ratio [OR] = 0.62, 95% CI: 0.53–0.72) (3). An independent additional systematic review of the literature confirmed this finding (OR = 0.58, 95% CI: 0.48–0.69) (4) and results from subsequent observational studies not included in these 2 meta-analyses gave similar results (5–7). Of relevance here is that it would be simplistic to infer observations obtained in the ART setting to natural conception. On the one hand, they may underestimate the effects on natural fertility. For instance, studies on ART properly explore embryo implantation but do not inform on the detrimental effects on sperm transit (ART could even be a valuable treatment because of its capacity to overcome detrimental effects on sperm migration). On the other hand, women with CSDs requiring ART may be highly selected. Those conceiving naturally are not scheduled for ART. Unfortunately, investigating the impact of CSDs on natural fertility is methodologically challenging, and available evidence is biased and noninformative.

Noteworthy, CSDs are a common finding. The rate of women showing these defects varies between 24% and 70% if transvaginal sonography is used and rises to 56%–84% with sonohysterography (8). In some settings, it may be even greater (2). Overall, these impressively high rates suggest that CSDs are clinically unremarkable in most cases. The current challenges are therefore identifying the characteristics of the women who require treatment and then discerning the optimal therapeutic option to restore fertility.

Using a Delphi consensus methodology, Klein Meuleman et al. (9) suggested defining CSD when the sonographic demonstration of a niche (indentation of the uterine myometrium of at least 2 mm) is associated with the presence of at least 1 primary or 2 secondary symptoms. The former included postmenstrual spotting, pain during uterine bleeding, technical issues with catheter insertion during embryo transfer and secondary unexplained infertility combined with intrauterine fluid. The secondary criteria included dyspareunia, abnormal vaginal discharge, chronic pelvic pain, avoiding sexual intercourses, secondary unexplained infertility, secondary infertility despite ART, negative self-image and discomfort during participation in leisure activities. Therefore, considering the issue of infertility, women who should be considered affected and candidate for treatment include those with secondary unexplained infertility and those who had a complicated embryo transfer.

In these situations, hormonal treatment cannot be prescribed given the desire of parenthood. One must consider surgical correction and/or ART. Unfortunately, randomized controlled trials (RCTs) are scanty and not designed with fertility as a primary outcome (10, 11). Evidence is therefore inevitably weak. A pivotal RCT comparing laparoscopic resection with expected management is ongoing and will presumably provide valuable information (10). However, in the meantime, physicians are called for action. The issue is further complicated by the availability of different treatment options; hysteroscopic enlargement of the niche, vaginal or laparoscopic or laparotomic reconstruction of the scar, intrauterine insemination or in vitro fertilization (IVF). All of them may be of some help but are not optimal. Hysteroscopy enlarges the defect rather than correcting it (the impact on pregnancy course is uncertain), recurrence of the defect after surgical reconstruction (either vaginal or laparoscopic or laparotomic) is not rare, intrauterine insemination may be useful only if the niche perturbs sperm transit, and ART does not overcome the detrimental effects on embryo implantation (12, 13). Given this uncertainty, a shared decision-making approach with the woman that takes into consideration also local expertise is fundamental. In general, rushing straightly to ART without considering preliminary surgery is not ideal. Assisted reproductive technology is a long and expensive journey and considering surgery only once failure is ascertained (that can take several oocyte retrievals and embryo transfers) may affect patients’ adherence, ultimately hampering their chance to have an infant. Noteworthy, all listed surgeries do not expose patients to major risks and can therefore be considered also in the absence of robust evidence

In conclusion, CSDs can affect fertility. There is a clear biological rationale and evidence is consistent. Robust studies are now needed to identify women for whom the defect is clinically relevant and to disentangle the best modality to treat them.

PRO: Olivier Donnez, M.D., Ph.D.

Although WHO determined CS rates in excess of 10% do not improve neonatal outcome and maternal mortality (14), CS rates have widely increased to more than 30% in all areas of the world (15). Cesarean section is unfortunately associated with uterine morbidity with an often-visible scar at the level of the incision site. First described in 1961 by Poidevin (16), there is increasing evidence that those scars might be associated with variable symptoms (post menstrual spotting, dysmenorrhea, dyspareunia) including infertility (17).

We demonstrated that severe defects (residual myometrium thickness [RMT] <3 mm) are surrounded with significantly lower muscular density when compared with the adjacent myometrium surrounding cesarean scar without defect (18). Those less dense muscle areas might be unable to completely expel menstrual blood that could remain trapped in the scar and slowly released after menstruation, explaining post menstrual spotting. Blood retention could induce inflammation, leading to pain and deteriorating fertility (19, 20). That might explain why fertility may be decreased after CS. Gurol-Urganci et al. (21) evaluated the impact of CS on subsequent pregnancies in a meta-analysis including 10 studies and found that patients who had undergone a CS had a 9% lower subsequent pregnancy rate and 11% lower birth rate, compared with patients who had delivered vaginally. In a population-based study on 1, 047, 644 women, the birth rate was lower by 19% after elective CS and by 9% after emergency CS (22).

However, little evidence is available concerning the way to manage what Klein Meuleman et al. (9) define as CSDs, also often called isthmocele. Association of estrogen and progesterone could prevent recurrent bleeding in more than 80% of women in 2 series of, respectively, 11 and 23 patients presenting CSD (23, 24). Conversely, the levonorgestrel intrauterine device was found to be effective in 88.3% of patients when treating CSD-related intermenstrual bleeding (25, 26), with 78.6% intermenstrual bleeding improvement within the first year of placement. Moreover, in a randomized, open label-controlled trial on 208 patients, Zhang et al. (27) reported that the levonorgestrel intrauterine system was superior to hysteroscopic resection for reducing spotting from 9 months onward, as well as the absolute number of spotting days from 6 months onward and pelvic pain from 3 months onward.

If hormonal treatments may be useful to help those who do not wish to become pregnant, such treatments are not an option when pregnancy is desired. In case of failure of or contraindications to medical treatment, surgery should be discussed according to the severity of symptoms, including infertility, the desire to preserve the uterus, the size of the CSD and RMT value. In such cases, the only way to correct CSD remains surgery (hysteroscopic resection or laparoscopic/abdominal/robotic/vaginal repair) (28).

Starting in the early 90s, different techniques of hysteroscopic resection of cesarean scar were found to improve symptoms. Such improvements were confirmed through other series and RCTs (17, 28). Between 59.6% and 100% of patients usually become pain free and post menstrual spotting free after hysteroscopic resection (17, 28), but Wang et al. (29) recorded an 86.6% failure rate in case of retroverted uteri in a series of 57 patients. In a randomized trial of 102 patients comparing hysteroscopic resection and expectant management, Vervoort et al. (30) observed a significant decrease in menstrual blood loss and improved quality of life after resection, but no impact on intermenstrual bleeding or dysmenorrhea compared with expectant management (30). These results can be explained by the variability of surgical techniques used (17, 28).

Our team described the laparoscopic repair of wide and deep CSD in 2008 (31), with a first study on 13 patients (32), followed by bigger series (4, 5). Laparoscopy allows to conduct a complete exploration of the pelvis and offers a direct access to CSD, enabling adhesiolysis if adhesions are present. In a series of 38 patients operated on by laparoscopic repair, all but 3 patients, all of whom had experienced pain and/or bleeding before surgery, were free of symptoms (18). We thus observed a 92% rate of symptom relief among the 33 patients presenting with pain and/or bleeding.

This technique also restores a thicker RMT (9.65 ± 1.77 mm) (18). Among the 18 patients from this series (18) consulting for infertility alone (n = 5) or infertility associated with pain and/or bleeding (n = 13), 8 (44.4%) became pregnant, and all of them delivered healthy infants by CS at 38–39 weeks of gestation. Pregnancy rates after surgery varies from 21.8% to 75% in other series (18, 28). However, the cohorts of patients are not comparable because of the disparity in techniques used and available information on subsequent pregnancies. After surgical correction of the defect, all of patients from our series could become spontaneously pregnant suggesting that surgery might also restore fertility in a group of patients presenting no other infertility factors. The median age of the patients included in this series was 32.6 ± 5.6 years old. Twenty-five of them had undergone 1 CS, 12 had undergone 2 CSs, and 1 had undergone 3 CS. Only 1 patient had experienced a vaginal delivery, followed by 2 CSs. Patients were selected according to their symptoms (bleeding, pain, or infertility) and the presence of a remaining myometrium measuring less than 3 mm at magnetic resonance imaging (MRI) evaluation with a median of 1.4 ± 0.7 mm. All the women underwent transvaginal sonography and MRI to preoperatively evaluate the defect and thickness of the remaining myometrium. All the patients were discharged from the hospital within 24 hours of surgery. After 3 months and subsequent pelvic MRI, the women were told they could attempt pregnancy.

In conclusion, when surgery is indicated for isthmocele, the choice between hysteroscopic resection and laparoscopic repair should be guided by RMT. Hysteroscopy is considered to be more of a resection than a repair, so women who desire pregnancy should not in our eyes be offered this technique when RMT <3 mm. In this instance, repair is essential and can only be achieved by a laparoscopic (or vaginal) approach. Although both techniques are associated with good anatomical results, laparoscopy allows the surgeon to explore other causes of infertility and pain, enabling simple correction of uterine retroflexion.

CON: Isthmocele should be observed

Leigh A. Humphries, M.D., M.S.C.E

Divya K. Shah, M.D., M.M.E.

Although we have a hammer, not every isthmocele is a nail. Although it may be tempting to correct every isthmocele seen on diagnostic imaging, reproductive surgeons should remain judicious and exercise evidence-based judgment when indicating a patient for surgery. There are 3 primary reasons one may choose to repair an isthmocele: (1) to treat symptoms of bleeding or pain; (2) to manage secondary infertility; and (3) to prevent adverse obstetric outcomes such as uterine rupture. We will consider the arguments and evidence for each of these indications individually.

Surgical repair of isthmocele can relieve symptoms of persistent postmenstrual bleeding and pelvic pain, with approximately 80%–100% of patients reporting symptom improvement or resolution after hysteroscopic, laparoscopic, or vaginal resection (33, 34). For patients who are not trying to conceive, medical management with hormonal therapy is also highly effective and should be prioritized (17). However, many isthmoceles represent incidental findings because most patients with isthmocele are asymptomatic (8). For example, about 44%–84% of patients with a history of cesarean delivery have isthmocele detected on sonohysterogram, regardless of symptom presentation (8, 17, 35, 36).

Secondary infertility is frequently proposed as an additional indication for isthmocele repair. Patients with isthmocele are known to have lower live birth rates after IVF/intracytoplasmic sperm injection as compared with those without isthmocele (adjusted odds ratio 0.62; 95% confidence interval 0.53–0.72) on the basis of a recent meta-analysis (2, 3). There are several theories to explain this. Accumulation of blood and mucus in the defect may be directly embryotoxic, may cause inflammatory changes that impair endometrial receptivity and sperm function, or may create a physical barrier to implantation (37). Histopathologic examination shows cystic dilatation and fibroblastic stromal reaction in the defect, with production of mucus and debris (38). Up to 40% of patients with an isthmocele also develop intracavitary fluid during ovarian stimulation cycles, which is associated with lower IVF treatment success if present at embryo transfer (39). This fluid can self-resolve, and pregnancy and live birth outcomes are comparable to those with no isthmocele if there is no visible fluid retention at the time of transfer (39). The indication for surgery may therefore seem obvious: eliminate the defect and enable the efflux of trapped debris and inflammatory contents.

Unfortunately, there is insufficient evidence to indicate that surgical repair of isthmocele improves fertility outcomes. Most studies addressing this question are low-quality, observational with small sample sizes, include inconsistent definitions and surgical techniques, and lack comparator groups for expectant management or fluid aspiration (12). A randomized trial in the Netherlands and a large prospective cohort study in France are currently underway and may provide useful clinical guidance in the future (10, 40). Currently, however, only a single randomized trial has been published examining surgical intervention in patients with infertility and isthmocele, which was defined as a defect ≥2 mm in depth with RMT ≥3 mm (41). At 1-year follow-up, the pregnancy rate was higher after hysteroscopic resection at 75% (n = 21/28), compared with 32% (n = 9/28) in those managed expectantly. Although these findings may be sufficient to recommend isthmocele repair in select candidates, one must avoid excessive extrapolation of these data, because both the ideal candidates for surgery and the optimal surgical approach remain unclear. Findings from a recent meta-analysis support this caution, concluding that more data are needed before isthmocele repair can be recommended in patients with or without infertility (42).

Given the shortcomings in the literature, some reproductive surgery centers, including our own, reserve surgery for candidates with persistent postmenstrual bleeding or pain, fluid accumulation on fertility workup or IVF cycles, and difficult or failed embryo transfers (43, 44). A large prospective cohort study has shown that patients with these indications as well as large isthmoceles (RMT <3 mm) have favorable ongoing pregnancy rates after laparoscopic repair—60.2% at 2-year follow-up for patients presenting with infertility, and 66.7% in those with no infertility (43).

There is a similar lack of evidence when it comes to the third indication for surgery—prevention of obstetrical complications. Prior studies have reported increased RMT after isthmocele repair as a surrogate marker of myometrial strength, although these have not been powered to detect differences in clinically meaningful outcomes, such as cesarean scar pregnancy, placental accreta spectrum disorders, and uterine rupture. Cesarean scar pregnancy occurs in about 1 in 2000 patients with a history of cesarean delivery, and it remains unknown whether isthmocele impacts this incidence (45). The location of implantation may be important, because a retrospective study of 17 patients found higher rates of placenta increta/percreta in pregnancies that implanted entirely within the isthmocele compared with those overlying a well-healed myometrial scar (46). Residual myometrial thickness has been associated with risk of uterine dehiscence or rupture in small cohort studies and case series, yet these studies are underpowered, subject to publication bias, and use variable outcome measures (44, 47). Because uterine rupture is rare and can only be assessed in the minority of patients who elect for trial of labor, many studies rely on the presence of an asymptomatic myometrial defect (also called uterine “dehiscence” or “window”) at the time of repeat cesarean delivery as a surrogate marker for uterine rupture (48). This may not constitute an adverse event and likely overestimates the risk of a thin myometrial layer. Finally, even if isthmocele is linked to increased risk of uterine rupture, it remains unclear whether surgical intervention to increase myometrial thickness results in healthier tissue capable of preventing adverse obstetric outcomes. It is also possible that aberrant healing, rather than RMT, can both result in isthmocele and predispose patients to rupture.

In summary, there is limited evidence that surgical correction of isthmocele improves patient prognosis, and the choice to pursue surgery should therefore be individualized. In many cases, an asymptomatic isthmocele may be expectantly managed and pregnancy safely pursued. Future research should focus on comparing reproductive outcomes with and without isthmocele repair and investigating the safety and efficacy of various surgical approaches.

CON: Mindy S. Christianson, M.D., M.B.A.

Dr. Howard W. Jones, a pioneer in reproductive medicine and surgery, significantly contributed to innovation in both IVF and reproductive surgery. Reflecting on the essence of medical progress, he reportedly once stated, “New ideas are not only the lifeblood of medicine, but they are its soul.”

The management of CS isthmocele defects exemplifies the evolution of surgical innovation, where advancements are acknowledged but hindered by systemic obstacles such as billing and coding challenges. Since Morris first introduced the term “isthmocele” in 1995 and the first laparoscopic repair of a CSD was documented in 2003, over 20 years have passed with limited high-quality research, restricting its integration into routine clinical practice (49, 50). Beyond the scarcity of robust data supporting the widespread clinical adoption of CS isthmocele repair, surgeons encounter significant challenges in implementing this procedure. Although 1 debate centers on whether CS isthmocele defects should be repaired, an equally important question is how readily the procedure can be performed and made accessible to patients. This perspective shifts the focus to the business of medicine, highlighting the practical and financial challenges that influence its availability. This side of the debate on whether CS isthmocele repair should be performed for women with infertility argues that CS isthmocele repair cannot be widely offered to patients until the key obstacles to its clinical adoption are resolved. Three primary barriers hinder its broader implementation: (1) Lack of standardization among surgical techniques, (2) limited educational opportunities available for teaching the surgical technique and (3) billing, coding and reimbursement challenges. Until these 3 areas are adequately addressed, CS isthmocele repair cannot be performed widely for women who may benefit from the procedure.

Lack of standardization

Currently CS isthmocele repair has been treated via 3 primary surgical approaches, hysteroscopic, abdominal/laparoscopic, and vaginally. There are no clear indications in the literature regarding which technique is optimal for a given clinical scenario (51). Although hysteroscopic treatment of a CS isthmocele is the least invasive of the 3 types of treatment, it is a resection of the CS defect so the RMT must be considered. Three studies have reported that hysteroscopic resection of isthmocele significantly increases RMT, although the improvement is less pronounced than with laparoscopic correction. Pregnancy rates after hysteroscopic resection vary widely, from 6.6% to 100%, likely because of the observational nature and small sample sizes of these studies (52–54).

Vaginal excision of isthmocele involves removing the defect and performing a double-layer uterine closure, which has been shown to increase RMT. Studies report persistence of isthmocele in 13% to 31.37% of cases (24, 55). Laparoscopy allows visualization of the entire pelvis and precise resection of fibrotic tissue after dissection of the bladder, with the uterus then closed in 1 to 2 layers. Studies to date report an increased residual endometrial thickness, and live birth rates range from 21.8% to 75% (24, 56, 57). For all 3 techniques, variability in surgical techniques creates inconsistencies in outcomes and limits procedural reliability and the ability to identify a first-line technique as well as clear criteria for which technique to perform.

Limited educational resources

Inadequate training opportunities for diagnosing and repairing isthmocele defects hinder skill development among surgeons. Because there is a lack of consensus regarding the best approach for a given patient scenario, this also limits teaching opportunities. Laparoscopic surgery can be more technically complex and therefore performed by a limited number of surgeons, whereas hysteroscopic isthmocele resection is not universally taught among surgeons. As a result, surgeons may choose a technique on the basis of their skill set rather than the optimal approach for the specific scar defect (58).

Billing, coding, and reimbursement challenges

Despite growing recognition of CS isthmocele as a clinical entity, billing and coding challenges may be the biggest hurdle preventing widespread adoption. Until October 2023, there was no specific diagnostic code for isthmocele in a gynecologic setting, making documentation and insurance claims difficult (59). The introduction of ICD-10 code N85.A (Isthmocele) for nonpregnant patients was a step toward legitimizing the condition, but a crucial gap remains: there is no dedicated Current Procedural Terminology (CPT) code for its surgical repair.

Without a formal CPT code, surgeons must rely on unlisted procedure codes, making reimbursement unpredictable and often requiring extensive justification to insurers. The American Medical Association (AMA) mandates that an unlisted code be carefully chosen on the basis of surgical complexity, approach, and anatomic site. Even then, insurers typically request comparable procedures with established relative value units to approximate payment, further complicating financial viability for hospitals and surgeons.

For isthmocele repair to become a mainstream procedure in the United States, a dedicated CPT code is necessary. However, the CPT Editorial Panel’s rigorous review process - requiring clinical data, procedural frequency, and physician consensus—means approval is neither quick nor guaranteed (60, 61). Until there are CPT codes for laparoscopic, hysteroscopic and vaginal isthmocele repair, the lack of standardized reimbursement will remain a significant barrier, preventing widespread adoption of this procedure in routine gynecologic practice.

In conclusion, although the recognition of CS isthmocele as a clinical condition has progressed, significant hurdles prevent its surgical repair from being ready for prime-time practice. The lack of standardized surgical techniques, limited educational resources, and the absence of a dedicated CPT code make widespread adoption impractical. Without clear guidelines on optimal surgical approaches and adequate training opportunities, procedural variability will continue to impact outcomes. Additionally, billing and reimbursement challenges create financial disincentives for hospitals and surgeons. Until these key issues are resolved, CS isthmocele repair will remain an evolving but inaccessible option, limiting its potential benefits for women with fertility challenges.

L’étude complète est disponible en anglais ici :

https://www.fertstert.org/article/S0015-0282(25)00155-4/fulltext